Pharmacokinetic Questions Prepared and collected By S.Bohlooli, PhD

Questions Mr Jones is admitted to General hospital with pneumenia due to gram negative bacteria. The antibiotic tobramycin is ordered. The Cl and Vd of tobramycin in Mr Jones are 80 ml/min and 40 l, respectively.

1) What maintenace dose must be adminstrated intravenously every 6 hours to eventually obtain average steady state plasma concentration of 4 mg/l? 0.32 mg 115 mg 160 mg 230 mg None of above

Rate In = Rate Out at steady sate Dosage = Plasma level(ss) x clearance Dosage = 0.32 mg/min Dosage = 0.32 mg/min x 60 min x 6 h Dosage = 115.2 mg/dose given at 6 hour intervals

0.1 mg 10 mg 115.2 mg 160 mg None of the above 2) If you wish to give Mr Jones a loading dose to achive the therapeuic plasma concentration of 4 mg/L rapidly, how much should be given? 0.1 mg 10 mg 115.2 mg 160 mg None of the above

Loading dose = Vd x Plasma Concentration Loading dose = 40 L x 4 mg/ L = 160 mg

1.6 days 2.4 days 3.2 days 4.8 days 6.4 days Despite your careful adherence to basic pharmacokintic priciples. Your patient on digoxin therapy has developed digitalis toxicity. The plasma digoxin level is 4ng/ml. renal fuction is normal and the plasma t1/2 for digoxin is 1.6 days. How long you should with hold digoxin in order to reach a safer yet probably therapeutic level of 1 ng/ml? 1.6 days 2.4 days 3.2 days 4.8 days 6.4 days

Once a day Twice a day Three times a day Four times a day Drug X has a narrow therapeutic index: the minimum toxic concentration is 1.5 times the minimum therapeutic plasma concentration. The half life is 6 hours. It is essential to maintain the plasma concentration above the minimum therapeutic level. Of the following, the most appropriate dosing regimen would be Once a day Twice a day Three times a day Four times a day Six times a day

After one half life(6 hours) Cp=75 uniuts Cp=150 units MEC = 100 units MTC = 150 Units After one half life(6 hours) Cp=75 uniuts Cp=150 units Cp=150 units Cp=100 units After 2/3 half life(4 hours)

Approximately 48 minutes Approximately 8 hours Approximately 5.8 hours The pharmacokinetics of theophylline include the following average parameters: Vd 35 L; CL 48 ml/min; half life 8 hours. If an IV infusion of theophylline is started, how long will it take to reach 93.76% of the final steady state? Approximately 6 hours Approximately 48 minutes Approximately 8 hours Approximately 5.8 hours Approximately 32 hours

Your patient with myocardial infarction has a severe cardiac arrhythmia. You have decided to give lidocaine to correct the arrhythmia.

40 mg/L 3.0 mg/L 0.025 mg/L 7.2 mg/L 3.46 mg/L A continous IV infusion of lidocaine, 1.92 mg/min, is started at 8 AM. The average pharmacokinetic parameters of lidocaine are: Vd 77 L; Cl 640 ml/min; half life 1.8 hours. The expected steady state plasma concentration is approximately 40 mg/L 3.0 mg/L 0.025 mg/L 7.2 mg/L 3.46 mg/L

Dosage = Cp (ss) x Clearance 1.92 mg/min = Cp(ss) x Cl

Your patient has been receiving lidocaine for 8 hours and you decide to obtain a plasma concentration measurement. When the results come back, the plasma level is exactly half of what you expected. The most probable explanation is The patient’s lidocaine volume of distribution is half the average The patient’s lidocaine clearance is twice the average The patient's lidocaine half life is half the average The patient infusion rate was accidentally decreased by half The laboratory made a mistake in the assay for lidocaine

3 mg/L 4 mg/L 6 mg/L 9.9 mg/L 15 mg/L A patient requires an infusion of procainamide. Its half life is 2 hours. The infusion is begun at 9 AM. At 1 PM the same day a blood sample is taken; the drug concentration is found to be 3 mg/L. what is the probable steady state drug concentration, after 48 hours infusion? 3 mg/L 4 mg/L 6 mg/L 9.9 mg/L 15 mg/L

From 9 AM to 1PM is 4 hours or 2 half lives Cp=50%Cpss at t= 1 half life Cp=75%Cpss At t= 2 half life Cp=0 at t=0 Cp=3mg/L 3mg/L = 75%Cpss

25 mg 50 mg 100mg 200mg Too few data to predict A narcotic addict is brought to the emergency room in a deep coma. His friends sate that he took a large dose of morphine 6 hours earlier. An immediate blood analysis shows a morphine blood level of 0.25 mg/L. assuming that the pharmacokinetics of morphine in this patient are Vd 200 L and half life is 3 hours, how much morphine did the patient inject 6 hours earlier? 25 mg 50 mg 100mg 200mg Too few data to predict

Amount of injected morphine = Vd x Cp 6 hours means 2 half lives 0.25 mg/L At t=2 half life 0.5 mg/L At t=1 half life 1mg/L At t=0 Amount of injected morphine = Vd x Cp = 200 L x 1mg/L = 200mg

The data are insufficient to answer Enalapril, an angiotensin converting enzyme inhibitor, has a half life of 3 hours, but is effective and nontoxic in most patient when given once a day, assuming IV administration, this indicates that the “ therapeutic window” for enalapril is at least 2 8 21 256 The data are insufficient to answer

Half life = 3 hours Dosing interval = 24 hour Plasma Concentration MEC MTC Peak Trough Time Plasma Concentration 256

A 65 years old man (weight 70 kg) is to be treated with amikacin for a gram negative sepsis. His renal function is approximately 50% of normal. Pharmacokinetic parameters of the drug (in an individual with normal renal function) include: Vd = 0.3 L/kg; CL = 80 ml/min; half life = 3 hours if you wish to establish an optimal drug level of 20 mg/L, rapidly, the loading dose should be approximately 6mg 60mg 200mg 400mg 600mg

Loading dose is independent of clearance And often renal function Loading dose = Vd x Cp =0.3L/kg x20 mg/ml =6mg/kg =6 mg/kg x 70kg =420 mg

Prednisolone plasma concentration decay after administration to a patient received transplant kidney

The plot of logarithm of ranitidine plasma concentration versus time