Pentoxifylline Extended-Release Tablets 4 mg COMPARATIVE BIOAVAILABILITY STUDIES APOTEX CORP.
Product: Pentoxifylline Extended-Release Tablets Approval Date: June 9, 1999 Indication: Description: treatment of patients with chronic occlusive peripheral vascular disease of the extremities white, oval, unscored, film-coated tablets, imprinted with "APO 33" on one side and plain on the other side COMPARATIVE BIOAVAILABILITY STUDIES OF APOTEX CORP. PENTOXIFYLLINE EXTENDED-RELEASE AND TRENTAL 4 mg TABLETS Study Design: Fasting Biostudy: Food Effect Biostudy: Steady State Biostudy: Standard 2-way cross-over bioavailability study Standard 3-way cross-over bioavailability study Standard 2-way cross-over steady state study Subjects: Normal human volunteers Normal human volunteers Normal human volunteers Number: 37 Number: 16 Number: 24 Mean Age: 28.3 years Mean Age: 27.8 years Mean Age: 32.3 years Mean Weight: 164.4 lbs Mean Weight: 16.4 lbs Mean Weight: 174.5 lbs Dose Administered: 4 mg (1 tablet) 4 mg (1 tablet) 4 mg (1 tablet) at, 8, 16, 24, 32, 4, 48, 56, 64, 72, 8, 88, and 96 hours Sampling At:,.33,.67, 1, 1.33, 1.67, 2, 2.33, 2.67, 3, 3.5, 4, 4.5, 5, 6, 8, 1, 12, 15, 18, 21, and 24 hours,.33,.67, 1, 1.33, 1.67, 2, 2.33, 2.67, 3, 3.5, 4, 4.5, 5, 6, 8, 1, 12, 15, 18, 21, and 24 hours Assay Method: LC/MS/MS LC/MS/MS LC/MS/MS Washout Time: 1 week 1 week 1 week, 24, 48, 72, 96, 96.25, 96.5, 97, 97.5, 98, 98.5, 99, 99.5, 1, 11, 12, 13, 14, 16, 18, 111, 114, and 12 hours
FASTING BIOSTUDY Pentoxifylline 9% Confidence Intervals * AUC -inf (ng hr / ml) 837.62 (36.) 84.31 (39.8).85-1.6 AUC -T (ng hr / ml) 665.34 (45.9) 681.72 (44.2).92-1.7 Cmax (ng / ml) 17.95 (47.8) 17.65 (42.3).9-1.11 Pentoxifylline 9% Confidence Intervals * AUC -inf (ng hr / ml) 3555.5 (37.9) 3518.99 (4.5).95-1.7 AUC -T (ng hr / ml) 3183.2 (38.1) 332.6 (42.4).93-1.6 Cmax (ng / ml) 393.8 (4.8) 41.5 (44.1).92-1.11 Pentoxifylline 9% Confidence Intervals * AUC -inf (ng hr / ml) 6338.4 (27.2) 6258.22 (27.7).97-1.13 AUC -T (ng hr / ml) 631.5 (23.6) 5913.49 (27.8).98-1.1 Cmax (ng / ml) 789.92 (25.9) 74.62 (31.4) 1.2-1.15 1 9 8 7 6 5 4 3 2 1 4 8 12 16 2 24 4 35 3 25 2 15 1 5 4 8 12 16 2 24 8 7 6 5 4 3 2 1 4 8 12 16 2 24
FOOD EFFECT BIOSTUDY AUC -T (ng hr/ml) 772.1 (74.2) 782.64 (72.1) 692.53 (72.8) 1. Cmax (ng/ml) 143.94 (77.8) 183.5 (72.) 128.59 (14.2).86 AUC -T (ng hr/ml) 3386.68 (69.1) 331.61 (73.1) 3249.98 (73.9) 1.3 Cmax (ng/ml) 53.91 (71.8) 594.88 (71.2) 446.6 (87.3).87 AUC -T (ng hr/ml) 6288.69 (23.7) 5934.6 (31.1) 5831.56 (28.) 1.1 Cmax (ng/ml) 933.38 (32.6) 998.44 (36.7) 833.31 (33.1).93 12 1 8 6 4 2 4 8 12 16 2 24 45 9 4 35 3 25 2 15 1 8 7 6 5 4 3 2 5 1 4 8 12 16 2 24 4 8 12 16 2 24
STEADY STATE BIOSTUDY 9% Confidence Intervals * AUC 96-14 (ng hr/ml) 62.7 (41.8) 593.15 (42.7).93-1.9 Cmax (ng/ml) 139.83 (51.5) 145.81 (55.3).82-1.11 9% Confidence Intervals * AUC 94-14 (ng hr/ml) 2494.33 (35.1) 2568.37 (33.7).88-1.4 Cmax (ng/ml) 462.92 (38.2) 471.58 (33.2).86-1.6 9% Confidence Intervals * AUC 96-14 (ng hr/ml) 6122.83 (27.7) 6538.54 (23.5).83-1.1 Cmax (ng/ml) 1178.71 (28.3) 1249. (22.).82-1.2 14 12 1 8 6 4 2 96 97 98 99 1 11 12 13 14 5 45 4 35 3 25 2 15 1 5 96 97 98 99 1 11 12 13 14 14 12 1 8 6 4 2 96 97 98 99 1 11 12 13 14