PHA5128 Dose Optimization II Case Study 3 Spring 2013

Transcription

1 Use the vancomycin dosing nomogram table below: A female patient, 57 years of age, 5 6 in height and 100 in weight had an infection requiring vancomycin treatment. Her serum creatinine was 0.8 mg/d. What would be the recommended initial dosage of vancomycin based on the nomogram above? Using this dosing regimen, compute the expected steady-state C max and C min values for both IV bolus administration and IV infusion (assuming 1 hr infusion time). Is the therapeutic goal attained (i.e. trough concentration between 15 and 20 mg/)? IBW = (height in inches 60) = (66 60) = 58.8 ABW = IBW + 0.4(TBW IBW) = ( ) = 75.3 We will use the adjusted body weight (ABW) given that the total body weight (TBW is more than 120% of the ideal body weight (IBW). Vancomycin is primarily cleared via the kidney. We can compute its clearance using the creatinine clearance estimation. C cr (female) = 75.3(140 57) 0.8(85) = 91.9 m/min Based on the nomogram, you will use 1000 mg q8h dosing regimen. To compute the steady concentrations, first transform the clearance to /h unit. C = 91.9 m min m 60min = 5.51 hr h V d = 0.17(age in yrs) (TBW in ) + 15 = 0.17(57) (100) + 15 =

2 k = C = 5.51 = h 1 V d 46.7 For IV bolus, C max,ss = For IV infusion, C max,ss = S F dose V d 1 1 exp( kτ) = 1(1)(1000) 1 mg = exp( ) C min,ss = C max,ss exp( kτ) = 35 exp( ) = 13.6 mg S F dose C 1 exp( kt) 1 exp( kτ) = 1(1)(1000) 1 exp( ) mg = exp( ) C min,ss = C max,ss exp( kτ) = 33.1 exp( ) = 14.5 mg Both steady C min for IV bolus and IV infusion are below the 15 to 20 mg/ range. Therapeutic goal is not attained. 2

3 While on vancomycin, a male patient, 46 years of age, 6 3 in height, weighing 147, had a loss of volume of distribution of 10% and a corresponding increase in serum creatinine level by 30%. Adjust his vancomycin dosage, assuming that his previous serum creatinine was 1.3 mg/d. The MIC of vancomycin against his infection was 0.5 mg/. Compute the steady state Cmax and Cmin based on IV bolus administration. With the dosing regimen that you have recommended, are the first dose Cmin and the steady state Cmin values consistently above MIC? Do you need to adjust the dosing frequency based on the computation that you have obtained so that the trough is below 25 mg/ and between 15 to 20 mg/? Estimate the AUC to MIC ratio of vancomycin for the patient s altered condition, assuming that vancomycin is administered as an IV bolus and follows a 1 compartment body model (Hint: use the equation AUC = C ss,max /k e to estimate this ratio. V d (in ) = 0.17(46) (147) + 15 = 55.2 New V d = 0.9 V d = 49.7 IBW = (75 60) = 84.5 ABW = ( ) = C cr,male = New C cr = (140 46) (1.3) = 110 min (140 46) = 84.6 min For both conditions, the recommended dosing regimen for vancomycin is 1000 mg q8h. No need to adjust his dosing regimen. C = 84.6 m min m 60min = /h h k = /h 49.7 = h 1 3

4 For IV bolus, C max,ss = mg = exp( ) C min,ss = 36.1 exp( ) = 16 mg The steady state trough concentration is below 25 mg/ and is within the 15 to 20 mg/ range. There is no need to change dosage. The AUC to MIC ratio is: The therapeutic goal is achieved. AUC = 36.1 = mg. h/ AUC MIC = = >

5 A female patient, 49 years of age, 78 in weight, is started on intravenous phenobarbital sodium. The normal therapeutic range for this medication is between 10 and 30 mg/. A loading dose was administered to achieve a drug plasma concentration at t=0 of 30 mg/. Calculate what the loading should be to achieve a target concentration of 30 mg/ and the daily maintenance dose to produce an average steady state phenobarbital concentration of 25 mg/. Note that the dose should be computed for phenobarbital sodium. V d = = 54.6 C = 4 m h The salt factor for phenobarbital sodium is 0.9. The compute the loading dose, D = MD = C C p τ F S m 78 = 312 h = 13 day V C = = 1820 mg ~ 2000 mg F S = 13 mg 25 day 1day = 361 mg ~ 400 mg/day Note that maintenance dose should be based on dose per day. 5

6 A 59 year old male patient of 87 weight is to receive carbamazepine regimen. Compute the daily oral dose (for immediate release formulation) to achieve an average steady state plasma concentration of 6.0 mg/, assuming monotherapy (i.e. no concomitant medication). In the second scenario, the same male patient received 1.5 mg/ by body weight phenobarbital q12h for the past 12 months without any success in controlling his seizures. The medical practitioner decided to start this patient on a concomitant therapy with carbamazepine. Compute the daily maintenance dose to achieve a target steady state concentration of 6.0 mg/ using the immediate release formulation. His blood sample after being on a maintenance regimen of carbamazepine showed a level of 11 mg/ carbamazepine. Compute the dose adjustment so that the patient gets the desired plasma concentration of 6.0 mg/. Carbamazepine C in monotherapy is / Dose = C p,ss C τ = F S For polytherapy, carbamazepine C is 0.1 / MD = = mg~1000 mg = 1566 mg mg ~1500 day day Using proportionality ratio to compute the dose adjustment, 11 mg 6 mg = 1500 mg x x = 818 mg ~800 mg 6