PHA 5127
Problem Set "Multiple Dosing"
1. Antiexamin is a drug against exam butterflies. It has a half-life of 3.5 days. It is given by i.v. injection every Saturday after the football game at a dose of presumably 200 mg. The plasma concentration directly after the first dose is 200 mg/ml (Cpo). To cure the symptoms a concentration above 100 mg/ml has to be maintained. Mark whether the following statements are true or false
during the first week after the injection, an exam should not be taken on Thursday.
the above indicated dose is not correct.
the plasma concentration just before the second injection will be 50 mg/ml
during the week of finals (Thursday) the student will be better protected than during the first week.
considering that the exams are given on workdays it would be better to give the drug on Friday night.
2. The population pharmacokinetics of the oral diuretic agent, chlorthalidone, for a 70 kilogram person are:
F = 0.64 (bioavailability)
V = 280 Liters
CL = 4.5 Liters/hour
Assuming that absorption is instantaneous relative to elimination, calculate the following when 50 mg dose of chlortalidone is taken daily at breakfast:.
a) The time required to achieve 50% of plateau.
b) The accumulation ratio (factor) at steady state.
3. Mark whether the following statements are true or false with regards to drugs given as a multiple-dose regimen.
the extend of accumulation (r) is affected by the volume of distribution.
the extent of accumulation (r) increases as the same dose of a drug is given less frequently.
at steady state, the amount of drug lost within a dosing interval equals the maintenance dose.
the larger the volume of distribution, the lower the average steady state concentration
the shorter the half-life of a drug, the higher the fluctuation between peak and trough.
4. A drug is given in an oral multiple-dose regimen. Mark the following ments true (T) or false (F):
accumulation always occurs
the extent of accumulation increases as the same dose of drug is less frequently given
at plateau (steady state) the amount of drug lost within a dosing interval equals the maintenance dose.
the larger Vd, the lower the average plateau concentration.
the average plateau concentration depends on the absorption kinetics.
5. Compared to drugs with a longer half-life, drugs that are rapidly eliminated (i.e., have a short half-life) will generally require a (the) Click here __________ to fill in the blank dosing interval.
a) shorter
b) longer
c) same
d) zero
6. Mark whether the following statements are true or false
The shorter the half life of a drug:
the larger the loading dose for an i.v. infusion
the lower the albumin binding
the larger the volume of distribution
7. The is used quite frequently to design repetitive intravenous injections. Mark whether following statements are true (T) or false (F)
is often taken as the mean between Cpssmax and Cpssmin
is : (Cpmax -Cpmin)/Cpmax*100
the longer the half-life, the smaller the dose per dosing interval to achieve a certain
is :Cpssmax/Cpssmin
is f*D/(Cltot*t)
8. What factors determine the difference between peak and trough values in repetitive dosing.
9. Mr. J.M. a non smoking 60 kilogram patient with asthma, is to be started on an oral regimen of aminophylline (85% of which is theophylline). The pharmacokinetics for a typical patient with this disease are:
F(bioavailability) = 1.0 (for theophylline); V = 0.5 L/kg;
Cl = 40 ml/hr/kg
Design an oral dosage form of aminophylline (100 and 200 mg tablets are available) for this patient to maintain a plasma concentration within the therapeutic window, 10-20 mg/liter. Assume complete absorption of theophylline.
10. A drug is given by repetitive i.v. injection. 50 mg of this drug are either given every 3 or 6 hours. Which of the following parameters differ between these dosage regimen:
Clearance, volume of distribution, Cpss(max), Cpss(min), AUC per dosage interval, accumulation factor (r), F, t (tau)
11. A certain drug is eliminated only by the kidney. The normal maintenance dose is typically 5 g/day, the loading dose is 10g. What loading and maintenance doses should be used in a patient with a creatinine clearance of 12.5 ml/min.
12. A patient receives intravenous Gentamicin every 8 hr. After steady state is reached, a peak concentration of 6.8 mg/ml is determined; the concentration 7 hr after the peak is 1.7 mg/ml. Estimate K for Gentamicin in this patient.
0.14 hr-1
0.20 hr-1
0.33 hr-1
0.38 hr-1
slope =
13. After drug administration, pharmacokinetic models are useful to describe plasma concentration-time profiles. Relate following profiles to the appropriate pharmacokinetic models.
PROFILES
Return to Problem Set List