# PHAR 7633 Fall 1999

## OU HSC College of Pharmacy

### Second Exam 12 November 1999

Section FOUR. 15 + 19 + 10 = 44 points

Show all your work for full credit. All material not deleted or crossed-out will be considered for grading. Do NOT use any linear or semi-log regression functions/features that might be on the calculator that you use during this exam.

Q4.1 Version A, D, Q4.2 Version B, Q4.3 Version C (15 points) Assuming a one compartment linear pharmacokinetic model, with kel = 0.16 hr-1 and V = 78 L, calculate the expected plasma concentration at 24 hours after the following IV bolus dose schedule: 200 mg at time 0 hr; 300 mg at 6 hr; 300 mg at 18 hours.

 Parameter A B C D kel 0.16 0.07 0.34 0.09 V 78 321 26 234 Dose1 200 100 300 100 Dose2 300 200 200 400 t2 6 6 6 6 Dose3 300 300 300 200 t3 18 18 12 12 Cp (mg/L) 1.74 0.85 0.22 0.68

Q4.2 Version A, D, Q4.3 Version B, Q4.1 Version C. (19 points) Calculate an appropriate dosing regimen for the following male patient; age = 67 years, weight = 74 kg, serum creatinine = 1.8 mg/ 100 ml (mg %). With this drug the kel is a function of creatinine clearance and previously determined values include: kel = 0.05 hr-1 with CLCr = 15 ml/min and kel = 0.12 hr-1 with CLCr = 60 ml/min. The apparent volume of distribution was 0.45 L/kg. Develop a dosing regimen to keep the peak concentration close to but below 6 µg/ml and the trough concentration below 1 µg/ml. Adjust tau to an appropriate value that is a multiple of 4 hours. Round doses to the nearest, appropriate 5 mg and calculate the expected maximum and minimum plasma concentrations.

 Parameter A B C D Sex M F M F Age 67 65 45 55 Weight 74 68 78 75 SCr 1.8 1.7 1.2 1.1 CLCr (ml/min) 41.7 35.4 85.8 68.4 kel1 0.05 0.04 0.05 0.05 CLCr1 15 15 15 15 kel2 0.12 0.15 0.19 0.15 CLCr2 60 60 60 60 knr 0.0267 0.0033 0.0033 0.0167 b 0.00156 0.00244 0.00311 0.00222 kel (hr-1) 0.0915 0.0899 0.270 0.169 V 0.45 0.25 0.3 0.22 Cpmax 6 8 8 6 Cpmin 1 1 0.5 0.5 R 0.167 0.125 0.0625 0.0833 tau (hr) 19.6 23.1 10.3 14.7 tau' (hr) 20 24 12 16 R' 0.160 0.116 0.0391 0.0673 MDose (mg) 168 120 180 92.3 LDose (mg) 200 136 187 99 MD' (mg) 165 120 175 90 LD' (mg) 195 135 185 95 Cpmax' (mg/L) 5.90 7.98 7.78 5.85 Cpmin' (mg/L) 0.947 0.923 0.304 0.393 Cpmax' (mg/L) 5.86 7.94 7.91 5.76

Q4.3 Version A, D, Q4.1 Version B, Q4.2 Version C. (10 points) A drug is to be given orally every twenty four hours to achieve an average concentration of 30 mg/L. Calculate the dose (F = 0.80) required if t1/2 = 12 hours and V = 32 L. Round your answer to the nearest 25 mg. Estimate the average, peak and trough concentrations after steady state is reached, using the rounded dose.

 Parameter A B C D Tau 24 12 12 24 Cp(bar) 30 15 20 25 F 0.8 0.9 0.7 0.8 t1/2 12 16 7 12 kel (hr-1) 0.058 0.043 0.099 0.058 V 32 123 15 27 Dose (mg) 1664 1066 509 1170 Dose' (mg) 1675 1075 500 1175 Cp(bar) (mg/L) 30.2 15.1 19.6 25.1 Cpmin (mg/L) 14.0 11.5 10.2 11.6 Cpmax (mg/L) 46.5 18.7 29.1 38.6