Case studies I

IV dosing  AUC, volume of distribution , clearance, elimination rate constants

 

  1. Your friend attempted suicide by taking an unknown quantity of acetaminophen.  At the E.R., his stomach is pumped and he is stable, however he is being considered for therapy with the antidote (N-acetylcysteine) for acetaminophen overdosing. This antidote is recommended if the serum acetaminophen concentration 4 h after the ingestion is > 200 ug/mL.   The overdose  is reported to have occurred at 10 AM (1000); at 4:00 PM (1600) his serum acetaminophen level was  48.9 ug/mL, and at 6:00 (1800) the same day  it is  27.8 ug/mL.  The apparent volume of distribution is approximately 0.75-1.0 L/kg.   The patient weighs about 60 Kg
    1. Should she receive N-acetylcysteine?

b.   Is this patient’s half-life consistent with the population average (2.5 h) or is there something unusual about his metabolism? 

c.   Estimate how many tablets the patient took Assume that absorption is extremely rapid because he took it on an empty stomach and the tablet strength was 500mg.

 

 

 

 

 

 

 

 

  1. A patient with advanced bone cancer with severe pain is given a 50 mg IV bolus dose of morphine.  From 0 to 3 hours after this dose of morphine,  the AUC is 5.1 mg-hr/L.  The total AUC is 22.4 mg-hr/L and the cumulative amount excreted unchanged is 11 mg
    1. What percent of the administered dose remains in the body as a drug at 3 hours?
    2. Calculate the total clearance
    3. Calculate the renal and metabolism clearance rates.

 

 

 

 

  1. A rare, inherited metabolic disorder has caused ammonia to build up in a girl's blood to levels that sent her into a coma and pushed her to the brink of death.   Plasma  concentrations of a new drug must be maintained  above 0.5 mg/L for 6 hours to strip the ammonia from her blood.  Given that a drug follows linear one compartment pharmacokinetics, with kel = 0.21 hr-1 and V = 230 L, calculate a suitable IV bolus dose to maintain therapeutic plasma concentrations. What is the initial plasma concentration?

 

 

 

 

 

  1. Following an acute seizure, 76 kg patient has received a 400mg  IV bolus dose of an anti- seizure drug.  The drug has the following pharmacokinetic population averages:  Vd= 2.3L/kg and half-life=12 hours.  The blood plasma concentration must be above 1 ug/ml for the drug to be effective.  When will the patient need another dose?

 

 

 

 

 

 

 

  1. When 100 mg of a drug was given as an IV bolus , the following plasma concentration – time relationship was found  (C is in mg/L and t is in hours)

C= 7.14 e(-0.173t)

Calculate        

            a.  the volume of distribution

b.     the elimination half life

c.      the total AUC

d.     total clearance

e.      plasma concentration 20 minutes after a 250 mg IV bolus dose