Effects of Vicoprofen and Ibuprofen on Anaerobic Performance After Muscle Damage

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1 Effects of Vicoprofen and Ibuprofen on Anaerobic Performance After Muscle Damage William J. Kraemer, Ana L. Gómez, Nicholas A. Ratamess, Jay R. Hoffman, Jeff S. Volek, Martyn R. Rubin, Timothy P. Scheett, Michael R. McGuigan, Duncan French, Jaci L. VanHeest, Robbin B. Wickham, Brandon Doan, Scott A. Mazzetti, Robert U. Newton, and Carl M. Maresh Objective: To determine the effects of Vicoprofen, ibuprofen, and placebo on anaerobic performance and pain relief after resistance-exercise-induced muscle damage. De-sign: Randomized, controlled clinical study. Setting: University humanperformance/sports-medicine laboratory. Participants: 36 healthy men. Methods and Measures: After baseline testing (72 h), participants performed an eccentric-exercise protocol. Each was evaluated for pain 24 h later and randomly assigned to a Vicoprofen (VIC), ibuprofen (IBU), or placebo (P) group. Postexercise testing was performed every 24 h for 4 d. Results: Significantly greater muscle force, power, and total work were observed in VIC than in P (P <.05) for most time points and for IBU at 48 h. Conclusions: Anaerobic performance is enhanced with VIC, especially within the first 24 h after significant muscle-tissue damage. The greater performances observed at 48 h might be a result of less damage at this time point with VIC treatment. Key Words: force production, injury, medical therapy, power Kraemer WJ, Gómez AL, Ratamess NA, et al. Effects of Vicoprofen and ibuprofen on anaerobic performance after muscle damage. J Sport Rehabil. 2002;11: Human Kinetics Publishers, Inc. Muscle soreness is a common occurrence after initiation of exercise or a sudden increase in the intensity of muscle activity. Delayed-onset muscle soreness arises hours after exercise, often with no identifiable injury, and can negatively affect muscle performance. Muscle damage and soreness have been linked to the eccentric phase of muscle activity with disruption of the contractile unit. 1 Few studies, however, have investigated the impact of muscle soreness on anaerobic performance. Muscle damage and soreness have a negative impact on athletic performance. Strength reductions of 50% to 60% have been reported after eccentric exercise with full recovery of muscle-force production taking Kraemer, Gómez, Ratamess, Volek, Scheett, McGuigan, French, VanHeest, and Maresh are with the Human Performance Laboratory, University of Connecticut, Storrs, CT Hoffman is with the Health and Physical Education Dept, College of New Jersey, Ewing, NJ Wickham, Doan, Mazzetti, and Newton are with the Biomechanics Laboratory, Ball State University, Muncie, IN

2 Vicoprofen and Performance 105 up to 2 weeks. 2,3 Power decrements have been reported during the initial days of football practice. 4 Vertical-jump height in these athletes appeared to be inversely related to muscle soreness. The magnitude of strength loss and time to full recovery might be related to the conditioning level of the individual, as well as the intensity of the eccentric stimulus. 5-7 The decline in physical performance, as well as the pain associated with muscle soreness, has led many athletes and medical professionals to examine a variety of interventions to mediate the damage associated with eccentric muscle activity and enhance recovery. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used with varying degrees of success. Some studies have shown a rapid return to activity after soft-tissue injury 8-11 with improvement in physical performance most likely being the result of decreased inflammation and pain. Not all studies, however, have shown a clinical benefit of NSAIDs for treating soft-tissue injuries Thus, the rationale for undertaking this study was to see whether a more potent pharmaceutical with an opiate and anti-inflammatory characteristics might improve the treatment results. Some evidence supports the premise that inhibition of the inflammatory process might actually delay healing by diminishing the regeneration of muscle fibers. 15 The disparity in demonstrated effectiveness with NSAIDs in treating muscle soreness clearly indicates the need for further investigation, and therefore this study was undertaken using the drug A combined opiate and anti-inflammatory medication appears to offer greater pain relief than an anti-inflammatory drug alone. The primary goal is a safe and rapid return to work or athletic endeavors. To date, few data exist on what happens to recovery during periods of continued physical activity. No data are available to address the influence of treatment interventions during a time of recovery in the face of activity and not complete rest. Pharmacological agents are often included in the treatment plan to decrease pain and inflammation associated with sports injuries and industrial injuries. To date, there have been no investigations to establish the effectiveness of the combination of hydrocodone with ibuprofen (Vicoprofen ) in treating soft-tissue injury after eccentric muscle damage. The purpose of this investigation was to compare the analgesic effects of Vicoprofen (hydrocodone bitartrate 7.5 mg with ibuprofen 200 mg), ibuprofen (200 mg), and placebo on anaerobic performance, pain relief, and return to performance during recovery after muscle damage, with recovery taking place in a continued demanding exercise en-vironment. Participants Methods Thirty-six men between the ages of 18 and 34 years participated in this study (see Table 1). All participants were carefully instructed on the design and procedures of the study, and each subsequently signed an informed-consent

3 106 Kraemer et al Table 1 Participant Characteristics* Age Height Body mass Body fat Treatment (y) (cm) (kg) (%) Vicoprofen (n = 12) 22.5 ± ± ± ± 5.6 Ibuprofen (n = 12) 23.0 ± ± ± ± 4.5 Placebo (n = 12) 22.8 ± ± ± ± 3.6 *Values are mean ± SD. document approved by the university s human use institutional review board. Medical-history and activity questionnaires were completed, and each potential participant was examined by a physician before the start of the study. Volunteers with medical disorders including orthopedic, neurological, metabolic, endocrine, or gastrointestinal disorders were excluded. Each participant completed a 3-day food diary and met with a registered dietitian for screening purposes. In order to limit the impact of dietary intakes on the results of the study (eg, excessive protein can lead to higher IGF-1 concentrations and changes in protein synthesis or degradation), all participants were determined to be within the normal ranges for nutrient intakes. None of the participants were college-level athletes, nor had any individual participated in organized competitive athletics for a period of at least 6 months before the study. Participation in recreational activities such as jogging, swimming, and aerobic dance was permitted. Lower body resistance training was not permitted, however, and could not have been part of the participants activity background over the past year. Study Design and Experimental Approach The design of this experiment was focused on determining the impact of Vicoprofen in comparison with placebo and ibuprofen on anaerobic performance after significant muscle-tissue damage in a demanding exercise environment for recovery. A randomized, double-blind, placebo-controlled, repeated-dose design was employed. Thirty-six men underwent baseline performance testing. Seventy-two hours later each participant performed eccentric exercise designed to elicit muscle damage. Twenty-four hours after the muscle-damage session participants returned to the laboratory and were evaluated for pain. Participants reporting mild or greater pain were randomized to 1 of 3 experimental groups (Vicoprofen, ibuprofen, or placebo) before postexercise testing. After this performance-testing session participants were instructed in taking the medication. They participated in postexercise testing every 24 hours (making up the continued demanding exercise environment for recovery) for 4 more days while on study medication.

4 Vicoprofen and Performance 107 Eccentric-Exercise-Damage Protocol One-repetition maximum (1RM) concentric knee-extension strength was determined at baseline for each participant in order to determine the loading required for the eccentric-exercise protocol. The exercise protocol performed on day 4 of the study was used to elicit muscle-fiber disruption (see Figure 1). Each participant completed 10 sets of 8 10 repetitions of eccentric knee extensions in a seated knee-extension weight-training device (Cybex, Ronkonkoma, NY) with a weight equivalent to 120% of the previously determined concentric 1RM per methods previously described by Dudley et al. 8 Briefly, to complete the eccentric exercise, investigators lifted the weight during the concentric phase and then asked each participant to slowly lower it to the starting position. The weight was adjusted for each set so that the participant could complete at least 8 repetitions and no more than 10 repetitions per set. In addition, the investigators observed the quality and velocity of the eccentric phase to ensure that each participant was reaching momentary muscle failure at the end of each set. Isokinetic-Strength Assessments Strength and fatigue testing were performed on the Cybex Norm isokinetic dynamometer, which enables the investigator to create a customized protocol that includes both concentric and eccentric tests. Throughout the strength and fatigue tests the participant was secured in the chair with a seatbelt and bilateral shoulder harnesses. The dynamometer arm was secured to his leg, 1 in proximal to the medial malleolus. Concentric knee-flexion and -extension and eccentric knee-extension strength were determined for each participant at baseline and daily after the eccentric-exercise session for a total of 5 days into the recovery period. Peak torque was determined for concentric knee flexion and extension at 360, 240,180, and 60 /s. Each participant received verbal encouragement to contract the muscles maximally. Three consecutive trials were performed at each velocity, and peak torque was recorded. A 3-minute rest period separated testing velocities. Figure 1 Timeline of the study identifying the visits to the laboratory (V), performance (Perf test), blood draws ( ), corresponding hours before or after the eccentric-exercisedamage protocol, and the visits during which Vicoprofen, ibuprofen, or placebo medications were administered (MEDS).

5 108 Kraemer et al Eccentric strength of the knee extensors was determined on completion of the concentric tests. Three trials were performed at 180 /s, and peak torque was recorded. Fatigue Test After the eccentric-strength test the participant rested 3 minutes, then completed 20 continuous repetitions of knee extension and flexion at 180 /s. Before beginning the test the participant was instructed to kick out and pull back as hard and as fast as he could. Throughout the 20 repetitions he received verbal encouragement to kick out and pull back. Power Determination A 30-second Wingate anaerobic power test was performed after a 5-minute rest period on completion of the isokinetic testing. This test was performed on a Monark cycle ergometer (Varberg, Sweden) on which pedaling resistance was manually adjusted to 7.5% of the participant s body weight. The cycle ergometer was interfaced with a PC computer, and data from flywheel revolutions were transformed into power data using customized software (SMI Power version , Sports Medicine Industries, St. Cloud, Minn). Peak power, mean power, and percent power decline were recorded. Visual Analog Scale Pain was assessed using a 10-cm linear visual analog scale (VAS) with labels of no pain and pain as bad as can be at either end of the scale. Participants marked their level of pain subjectively along the continuum. The distance in centimeters from the no-pain end was measured and reported as the raw score. Medication Medication was prescribed 4 times daily beginning with the day after completion of the eccentric-exercise protocol: Vicoprofen (VIC; hydrocodone bitartrate 7.5 mg with ibuprofen 200 mg, Knoll Pharmaceutical Co, Mt. Olive, NJ), ibuprofen 200 mg (IBU), or placebo (P). The first dose was administered at the end of testing on day 5. The remaining 3 doses were taken over the intervening 20-hour period, with the final dose taken 4 hours before the next testing session on day 6. Beginning with the sixth testing session and continuing over the remaining 4 days (through day 9), each participant received a new medication bottle with 4 tablets from which he took the first tablet in the presence of the study investigator 1 hour before the isokinetic and power tests. Blood Collection and Creatine Kinase Analysis Blood samples were collected before each testing session and on a daily

6 Vicoprofen and Performance 109 basis via venipuncture from the antecubital vein. Whole-blood samples were immediately analyzed for hematocrit and hemoglobin content and then were centrifuged, and the serum was aliquoted into separate tubes for storage at 85 C until further analyses were completed. Creatine kinase (CK) concentrations were determined using the colorimetric procedure (Sigma Chemical Co, St. Louis, Mo). Samples in which the rate of color development exceeded 0.5 absorbance units per minute were diluted with sterile saline, and an appropriate aliquot was used in the subsequent analysis. Intra-assay and interassay variances were less than 5% and 10%, respectively. Statistical Analyses The data presented represent the group mean (± SD) delta scores that were computed by a ranked-order procedure (ie, ranked IBU minus ranked placebo and ranked VIC minus the same ranked placebo). Briefly, this analysis approach allowed us to remove the ranked-placebo-level effect in order to see the effects of VIC and IBU and consisted of ranking the raw data for the 24-hour postdamage eccentric-extension exercise testing separately for each group. This was based on the fact that the damage protocol was the eccentric contraction, and this would be the most representative rank order to use to sort all the data and calculate the effects above a placebo level. After sorting the eccentric-extension exercise test data for each of the 3 groups, this identical sorting rank order was then used to calculate rank-order deltas for all data sets. Once all the data were sorted, a placebo-controlled delta (ibuprofen placebo and Vicoprofen placebo) was calculated for each variable. With mean placebo-controlled deltas determined for each variable, a repeated-measures analysis of variance (ANOVA) with Fisher LSD post hoc tests was used to compare the IBU and VIC groups over time (ie, 24, 48, 72, 96, and 120 hours after damage). Test retest reliability for the various dependent variables demonstrated intraclass correlation coefficients of R.95. Using the nquery Advisor software (Statistical Solutions, Saugus, Mass) the statistical power for the n size used ranged from.80 to.95. Statistical significance was chosen as P =.05. Results The 48-hour post-eccentric-protocol time point was the first at which medication had been administered for 24 hours. Demanding anaerobic assessments were administered each day, constituting an active and demanding exercise environment. This placed each recovery day into a context of continued stress typical for many athletes after soft-tissue injury. Therefore, the results must be examined within this experimental context and not one of passive recovery on each succeeding day. Significant increases in plasma CK were observed in all conditions (Figure 2). At 48 hours the concentrations for plasma CK (IU/L) were VIC, 2457 ± 1127; IBU, 4103 ± 1676; and P, 10,203 ± In direct comparison,

7 110 Kraemer et al CK was significantly lower (P <.05) in VIC than in IBU and P, and in IBU compared with P. At 72 hours, CK concentrations were significantly lower for IBU and VIC than for P. No differences were observed between P and either treatment condition at 24, 96, and 120 hours. The differences between IBU and VIC at 96 and 120 hours were significant, however. The results of the Wingate anaerobic power test are presented in Figure 3. At 48 hours, maximal power output was significantly higher in the VIC group than in the IBU and P groups. Maximal power output was significantly higher in VIC than in P through 120 hours and was significantly higher in IBU than in P only at 48 and 72 hours. Mean power was main- Figure 2 Comparison of the additive effects (placebo controlled) of Vicoprofen (VIC) vs ibuprofen (IBU) administration (200 mg) on serum creatine kinase concentrations (IU/L) at 24, 48, 72, 96, and 120 hours of recovery after eccentric-exercise-induced muscle damage. Values are mean ± SD, P =.05, vs corresponding IBU values. Figure 3 Comparison of the additive effects (placebo controlled) of Vicoprofen (VIC) vs ibuprofen (IBU) administration (200 mg) on peak and mean Wingate power outputs (W) at 24, 48, 72, 96, and 120 hours of recovery after eccentric-exercise-induced muscle damage. Values are mean ± SD, P =.05, vs corresponding IBU values.

8 Vicoprofen and Performance 111 tained significantly more in VIC than in both P and IBU at 48 and 72 hours. No significant differences were observed at 96 and 120 hours between any groups. VAS data are presented in Table 2. The difference in VAS scores for the squat test at 48 hours was statistically different between VIC and IBU. VIC was significantly higher, however, than IBU and P at 72 to 120 hours. Pain perception during the squat test after medication demonstrated a similar Table 2 Comparison of the Effects of VIC and IBU After Eccentric-Exercise-Induced Muscle Damage* Time Elapsed Action/ After Eccentric-Exercise-Induced Muscle Damage Treatment 24 h 48 h 72 h 96 h 120 h Conc ext, 240 VIC 8.3± ± ± ± ±15.3 IBU 12.3± ± ± ± ±15.3 Conc ext, 360 VIC 3.3± ± ± ± ±13.5 IBU 10.8± ± ± ± ±11.3 Conc flx, 240 VIC 2.3± ± ± ± ±8.2 IBU 6.5± ± ± ± ±9.0 Conc flx, 360 VIC 5.5± ± ± ± ±10.7 IBU 10.3± ± ± ± ±3.9 Ext % decline VIC 3.2± ± ± ± ±4.1 IBU 6.5± ± ± ± ±4.9 Flx % decline VIC 1.9± ± ± ± ±3.8 IBU 5.2± ± ± ± ±5.2 Isokinetic VAS VIC 0.2± ± ± ± ±1.2 IBU 1.5± ± ± ± ±1.1 Squat 1 VAS VIC 0.7± ± ± ± ±0.8 IBU 0.7± ± ± ± ±1.0 Squat 2 VAS VIC 0.1± ± ± ± ±0.6 IBU 0.7± ± ± ± ±0.6 Wingate VAS VIC 0.3± ± ± ± ±0.8 IBU 0.9± ± ± ± ±1.4 *VIC indicates Vicoprofen ; IBU, ibuprofen; Conc, concentric; ext, extension; flx, flexion; and VAS, visual analog scale. Values are mean ± SD. P.05 vs corresponding IBU value.

9 112 Kraemer et al response (see Table 2). Pain was significantly reduced at 72 and 120 hours in VIC compared with IBU and P after medication administration. The peak-torque data for concentric isokinetic knee extension performed at 60 and 180 /s are presented in Figure 4. These tests were performed for the leg with significant muscle damage. At 60 /s, peak torque was significantly greater in VIC than in P at 48 hours. At 120 hours, peak torque was significantly greater in VIC than in IBU. At 180 /s, peak torque was significantly higher in VIC than in IBU and P at 48 and 120 hours. At 240 and 360 /s (see Table 2), peak torque was significantly greater in VIC and IBU than in P, but no differences were observed between the 2 treatments. The peak-torque data for isokinetic knee flexion performed at 60 and 180 /s are presented in Figure 5. At 60 /s, peak torque was significantly greater in VIC than in IBU and P at the 48-hour time point. Significantly higher peak torque was observed in VIC than in P and in IBU than in P at each time point through 120 hours of recovery. At 180 and 240 /s (see Table 2), greater peak torque was observed in VIC than in IBU and P at the 48-hour time point. Peak torque was greater in both VIC and IBU than in P at all remaining time points, with the exception of 96 hours. At 360 /s, peak torque in both VIC and IBU was significantly higher than in P at all time points except 96 hours. Maximal eccentric-force-production data are presented in Figure 6. Maximal eccentric force was significantly greater in VIC than in IBU at 48 hours, and the mean value was higher in VIC than in IBU over the entire recovery Figure 4 Comparison of the additive effects (placebo controlled) of Vicoprofen (VIC) vs ibuprofen (IBU) administration (200 mg) on maximal concentric knee-extension torque (Nm) performed at 60 and 180 /s at 24, 48, 72, 96, and 120 hours of recovery after eccentric-exercise-induced muscle damage. Values are mean ± SD, P =.05, vs corresponding IBU values.

10 Vicoprofen and Performance 113 Figure 5 Comparison of the additive effects (placebo controlled) of Vicoprofen (VIC) vs ibuprofen (IBU) administration (200 mg) on maximal concentric knee-flexion torque (Nm) performed at 60 and 180 /s at 24, 48, 72, 96, and 120 hours of recovery after eccentric-exercise-induced muscle damage. Values are mean ± SD, P =.05, vs corresponding IBU values. Figure 6 Comparison of the additive effects (placebo controlled) of Vicoprofen (VIC) vs ibuprofen (IBU) administration (200 mg) on maximal eccentric knee-extension torque (Nm) performed at 180 /s at 24, 48, 72, 96, and 120 hours of recovery after eccentric-exercise-induced muscle damage. Values are mean ± SD, P =.05, vs corresponding IBU values. period. In addition, maximal eccentric-force production was greater in both treatment conditions than in P at all time points. Results of the 20-repetition fatigue test for both the knee extensors and flexors are presented in Table 2. The VIC group performed a significantly greater amount of work than did IBU at all time points during the kneeextension fatigue test. The percentage decline in force production was less than in P for both treatment conditions at all recovery time points from 48 hours onward. In the knee flexors, more total work was observed in the

11 114 Kraemer et al VIC group than in IBU at 48, 72, and 120 hours (data not shown). There was less of a reduction in force production in both treatments at the 48-, 72-, and 120-hour time points compared with P. The VAS pain data show that the greater total work accomplished in the VIC group resulted in a greater rating at 72, 96, and 120 hours. Comments The results of the present study indicate that administering Vicoprofen 24 hours after exercise results in a temporal maintenance of power and force production over the next hours. This window of adaptation provided the net benefit of Vicoprofen for continued performance within the active recovery period. At hours postexercise, plasma CK was significantly lower, possibly indicating less damage in the early phase of recovery. In addition, peak and mean anaerobic power and concentric and eccentric peak isokinetic torque of the knee extensors and flexors demonstrated improved performance with Vicoprofen compared with the ibuprofen and placebo alone. This maintenance of peak power and isokinetic torque was observed well into the recovery period (ie, at 96 and 120 hours). Muscle damage has been observed during exercise, primarily when a substantial eccentric component is involved. 1-4 One common indirect marker of muscle damage has been the level of the enzyme CK in the blood. 2-4 In the present study, plasma CK was significantly elevated in all groups after the muscle-damage protocol. The VIC group, however, showed significantly less increase in plasma CK than did the IBU or P group hours postexercise. It is important to note that it was necessary to produce maximal muscle damage in order to investigate the therapeutic hypothesis presented in this study. The aim was to investigate temporal effects on physical performance on subsequent days after muscle damage. The need for such performance maintenance is often vital in sport and work in order to meet the demands of the contest or job. Our results demonstrated that significant muscle damage was produced, as evidenced by the high values of plasma CK 24 hours after the exercise stress. Vicoprofen, and at some time points ibuprofen, however, were effective for limiting plasma CK concentrations or reducing the subsequent magnitude of muscle damage over the treatment period. The added benefit from Vicoprofen was observed in the performance tests, most likely as a result of less damage to the contractile unit. 8 It appeared that the reduction in muscle damage was critical to performance maintenance. The biochemical mechanisms that mediated the differences in muscle damage (eg, free-radical effects) with treatment remain unclear and require further examination. The Wingate anaerobic power test was used to determine peak and mean power output in the presence of significant muscle damage. After 24 hours of medication (ie, the 48-hour time point), participants in the VIC group

12 Vicoprofen and Performance 115 produced significantly higher peak power output than did IBU and P. On subsequent days, peak power performance was maintained above P up to 120 hours. In addition, peak power was maintained to a greater extent in IBU than in P at 48 and 72 hours, demonstrating that ibuprofen does contain an active component of Vicoprofen. It is likely that the maintenance of peak power in both treatment groups was a result of reduced muscle damage, leading to a greater number of motor units that could be normally involved with the recruitment process. The Wingate anaerobic power test elicits a high glycolytic stress with lactate concentrations surpassing 10 mmol/l. Thus, participants must be able to perform maximally with disruption to the contractile unit 6 and, in addition, cope with the high acidity, which in itself is a source of free-radical formation as a result of muscle hypoxia. Therefore, it was significant that the VIC group was able to produce the highest peak power within the first 24 hours of medication and maintain a higher level over the subsequent 4 days. Again, the interaction with a host of biochemical mechanisms to mediate such effects remains to be demonstrated. Thus, the benefit of Vicoprofen appeared to manifest to the greatest extent at the 48-hour time point, showing an advantage of potentially minimizing muscle damage and maximizing performance during a physically active recovery period. Mean power output was also maintained significantly more in VIC than in P and IBU at 48 hours. This effect was observed at 72 hours, as well. Neither VIC nor IBU differed from P at the 96- and 120-hour time points, indicating that the accumulated trauma from the active exercise during the recovery period did not allow for the intact muscles to continue to withstand the perturbations of exercise over the entire 4 days. The challenge of maintaining a higher mean power output over 30 seconds with significant muscle damage is overwhelming. The price of this higher mean power output in the VIC group resulted in no greater perception of pain at 48 hours, suggesting that the dissipation of pain, despite the greater amount of work and power output with damaged muscle, might well have been the mediating effect for the operational mechanism of Vicoprofen. The improvement in physical performance appears to most likely be the result of this decreased pain response. The ultimate cost of the higher amount of peak and total work done during the recovery period by the VIC group in all of the tests can be seen in subsequent days with a progressive increase in the pain scores as more force and more work were being accomplished. The offsetting of the negative effects of glycolytic metabolism with Vicoprofen appears to provide for an effective edge for a specific window of time during which continued maximal-effort physical activity continues. This places the data into an applied scenario where athletes, recreational enthusiasts, and heavy laborers continue to be active despite soft-tissue injury. Our data indicate that a combined opiate and anti-inflammatory medication appears to offer greater pain relief than an anti-inflammatory drug alone during the early

13 116 Kraemer et al phase of tissue-injury recovery At 60 /s, VIC had greater peak torque than did P at 48 hours and at 120 hours was significantly higher than in IBU. The 48-hour enhanced capability was similar to the improved power produced in the maximal-power test. These data imply higher force production at low speeds of muscle action in which the greatest peak torque is produced with the utilization of the greater number of motor units in the damaged musculature. As the speed of movement increased to 180 /s, the ability of the knee extensors continued to show a significant difference above not only P but also IBU. It is interesting to note that these values above IBU were also observed at 120 hours. At higher speeds (eg, 240 and 360 /s), both treatments were more effective than placebo, but no differences between the 2 treatments were observed. High velocities of muscle action recruit a greater number of fast-twitch motor units, and pain relief appears to be reflected in these data. In the present study, the hamstrings were not directly damaged by the protocol but worked as a contractile unit with the damaged quadriceps. At the 48-hour time point VIC produced significantly greater torque than IBU and P. The Vicoprofen treatment condition was higher than placebo and ibuprofen and was higher than placebo at each of the recovery time points measured over 120 hours. It was interesting that the treatment would affect the antagonist muscle group of the damaged tissue. It is thought that greater torque is produced as a result of the enhanced ability of the quadriceps to relax while the hamstrings are contracting maximally. This reduction in coactivation means that the contractile unit is able to function as it normally would under conditions of maximal effort. This phenomenon continues with Vicoprofen more than ibuprofen and placebo at the 48-hour time point with increasing velocity of movement at 180 and 240 /s. At these 2 higher velocities both treatment conditions produced greater torque than placebo at all time points except for 96 hours. At the highest velocity of hamstring movement (360 /s) both VIC and IBU were significantly higher than P at all time points except for 96 hours. The importance of allowing greater hamstring force production relates to both high-speed activities in sprinting and other high-speed movements. The Vicoprofen treatment produced significant treatment effects again at the 48-hour time point and was consistent with all the other force-production testing in this investigation. Eccentric-force production was greater in the VIC group than in IBU at the 48-hour time point, and the mean value was higher than in IBU over the recovery period. In addition, eccentric-force production was greater in both treatment conditions than in P at all time points. These data are striking because of the fact that using maximal eccentric muscle actions produced additional damage over the recovery period (see P-group CK) as part of the entire activity profile undertaken each day with testing. The ability of the Vicoprofen treatment to allow for superior force production in the damaged tissue using eccentric muscle actions is unique in the scientific literature. Again, the mediating mechanisms remain to be documented, but pain relief and reduced muscle damage from chemical insults over the recovery time

14 Vicoprofen and Performance 117 period appear to be the most likely mediators. The VIC group was able to perform more work in the 20 concentric isokinetic repetitions than was IBU at all time points for knee extensions. The percentage decline in force production was less than in P for both treatment conditions at all recovery time points from 48 hours onward. The ability of the VIC group to perform more total work than both IBU and P was important in light of the functional capacity of the damaged quadriceps. For knee flexors, more total work was achieved in the VIC group than in IBU at 48, 72, and 120 hours. There was less of a reduction in force in both treatment groups at the 48-, 72-, and 120-hour time points. It is believed that the ability of the hamstrings to perform more total work under Vicoprofen treatment is a result of the greater relaxation of the quadriceps contractile unit as an antagonist in this testing scenario. This was impressive because the quadriceps had been damaged, and no reduction in stress was observed during the intense activity of the recovery period. The VAS pain data showed that the greater total work accomplished in the VIC group did result in a greater pain rating at the 72-, 96-, and 120-hour time points. This might not be unexpected because of the much higher total work and peak force produced by the VIC group. Thus, the greater effort permitted by the treatment was perceptually challenging and comparable to that of the P group. This study was the first to examine the influence of pharmacological treatment regimes and the recovery of force production during an active recovery period similar to the real-life demands of sport and work. In summary, a primary emphasis in the treatment of athletes and physically active people at play or work is the pressure of returning them to play (or work) in a most expeditious manner without a loss in performance capability. This is especially true in competitions that take place after the initial injury has occurred. Members of the sports-medicine team (eg, physician, physical therapist, athletic trainer, exercise physiologist) work together in formulating the most comprehensive rehabilitation program. Pharmacological agents are often employed to decrease both inflammation and pain from sports injuries. 20,21 Considering the beneficial effects of the combination of hydrocodone and ibuprofen in the treatment of acute pain, it is thought that this combination might be particularly effective in treating athletes (both competitive and recreational). To date, these are the first data to demonstrate the effectiveness of Vicoprofen in treating acute soft-tissue injury in the context of an active recovery environment. The VIC group had distinct advantages in force, power, and total work production above P at most time points. It appears that this treatment advantage manifests above IBU at the 48-hour time point. This study design used a set of maximal tests each day of recovery, similar to conditions for athletes or workers who continue to have to perform or work in their daily jobs. Thus, the recovery data must be placed in the unique context of continued stress and damage activities over the

15 118 Kraemer et al 4-day period. The significantly higher strength and power capabilities also produced some higher pain ratings after the 48-hour time point, which is most likely a result of greater force production with less muscle-tissue mass (greater force per cross-sectional tissue). The ability of the damaged muscle to better relax in a cocontraction phenomenon in the VIC group was also a unique finding of this study. Nevertheless, there is a valid benefit added for anaerobic function with the use of Vicoprofen, especially within the first 24 hours after significant muscle damage. Acknowledgments The investigators would like to thank a dedicated group of test subjects for their efforts in this study. In addition, we would like to thank the physicians and laboratory staffs who all worked so hard in the process of this study. This study was funded in part by a grant from Knoll Pharmaceutical Inc, Mount Olive, NJ, which is now Abbott Laboratories, Abbott Park, Ill. References 1. Armstrong RB. Initial events in exercise-induced muscular injury. Med Sci Sports Exerc. 1990;22: Clarkson PM, Kosaka K, Braun B. Muscle function after exercise-induced muscle damage and rapid adaptation. Med Sci Sports Exerc. 1992;24: Clarkson PM. Eccentric exercise and muscle damage. Int J Sports Med. 1997;18: S314-S Smith ME, Jackson CGR. Delayed onset of muscle soreness (DOMS), serum creatine kinase (SCK), and creatine kinase-mb (percent CK-MB) related to performance measurements in football. Med Sci Sports Exerc. 1990;22:S Evans WJ, Meredith CN, Cannon JG, et al. Metabolic changes following eccentric exercise in trained and untrained men. J Appl Physiol. 1986;61: Smith LL. Causes of delayed onset of muscle soreness and the impact on athletic performance: a review. J Appl Sport Sci Res. 1992;6: Tiidus PM, Ianuzzo CD. Effects of intensity and duration of muscular exercise on delayed soreness and serum enzyme activities. Med Sci Sports Exerc. 1983;15: Dudley GA, Czerkawski J, Meinrod A. Efficacy of naproxen sodium for exercise-induced dysfunction, muscle injury and soreness. Clin J Sport Med. 1997;7: Hasson SM, Daniels JC, Divine JG, et al. Effect of ibuprofen use on muscle soreness, damage, and performance: a preliminary investigation. Med Sci Sports Exerc. 1993;25: Hutson MA. A double-blind study comparing ibuprofen 1800 mg or 2400 mg daily and placebo in sports injuries. J Int Med Res. 1986;14: Van Heerden JJ. Diclofenac sodium, oxyphenbutazone and placebo in sports injuries of the knee. S Afr Med J. 1971;52:

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