PHAR 7633 Fall 1999

Pharmacokinetics

OU HSC College of Pharmacy

First Exam 1 October 1999

Section THREE. Short Answer 4 x 5 = 20 points

Remember to limit the time spent on this section.

Q 3.1 Version A. Q 3.2 Version D. Briefly describe the parameter infusion rate constant. Give a definition, a working (useful) equation and units.
The infusion rate constant, k0 (usually zero order) gives the rate at which a drug may be infused IV into the blood stream. Units amount per time; e.g. mg/hr.
Equation: Cp^ss = k0/(kel x V)
or k0 = Cp^ss x kel x V

Q 3.1 Version B. Q 3.4 Version C. Briefly describe the parameter F. Give a definition, a working (useful) equation and units.

Parameter F is the bioavailability of a doage form. It is the extent or fraction of the dose that is absorbed into the blood stream. No units as the parameter is a fraction.
F = (AUC^A/AUC^B) x (DOSE^B/DOSE^A) x ...
F = (kel x AUC x V)/Dose if you have kel and V from IV data

Q 3.2 Version A, B, C. Q 3.1 Version D. Briefly describe the factors you would consider when comparing two different models. That is, how would you decide that one model was better than the other.
a) Parameter C.V.'s - too large -> smaller model
b) 'U' or '/' in weighted residual versus time plot -> more parameters or larger model
c) AIC - lower value better
d) F-test - calculated versus tabled
e) Systematic deviations on Cp versus time plot may mean a bigger model is needed

Q 3.3 Version A. Briefly describe the advantages and disadvantages of the sublingual or buccal route of drug administration.
Advantages: avoids first pass, rapid absorption, neutral pH (more stable)
Disadvantages: Small dose, taste may be bad, inconvenient, advantage lost if swallowed

Q 3.3 Version B. Briefly describe the advantages and disadvantages of the intramuscular route of drug administration.
Advantages: can give larger doses or volumes (compared with SC), depot of sustained release effects possible, by-pass first pass metabolism
Disadvantages: trained personal needed, site of injection affects absorption, absorption may be erratic and/or incomplete, painful, not easily reversed

Q 3.3 Version C. Briefly describe the advantages and disadvantages of the oral route of drug administration.
Advantages: convenient, portable, easy to take, cheap (relatively), compact, variety
Disadvantages: sometime inefficient, low solubility and/or high dose drugs, subject to first pass effect, food interaction, GI motility effects absorption, not suitable for unconscious patient

Q 3.3 Version D. Briefly describe the advantages and disadvantages of the rectal route of drug administration.
Advantages: partially avoids first pass effect, can be given to uncoscious patients or other unable to swallow oral medication
Disadvantages: erratic absorption, not well accepted

Q 3.4 Version A, B, D. Q 3.1 Version C. Briefly describe the important characteristics of subjects you may wish to use in a bioavailability study.
Age - 18 -35 yr
Weight - Appropriate for height
Enzyme status (smoker vs non-smoker, food or drug interaction)
Number (sufficient to see effect if present)
Health (healthy volunteers)

Q 3.1 Version A. Q 3.2 Version D. Briefly describe the parameter infusion rate constant. Give a definition, a working (useful) equation and units.	The infusion rate constant, k0 (usually zero order) gives the rate at which a drug may be infused IV into the blood stream. Units amount per time; e.g. mg/hr. Equation: Cp^ss = k0/(kel x V) or k0 = Cp^ss x kel x V
Q 3.1 Version B. Q 3.4 Version C. Briefly describe the parameter F. Give a definition, a working (useful) equation and units.	Parameter F is the bioavailability of a doage form. It is the extent or fraction of the dose that is absorbed into the blood stream. No units as the parameter is a fraction. F = (AUC^A/AUC^B) x (DOSE^B/DOSE^A) x ... F = (kel x AUC x V)/Dose if you have kel and V from IV data
Q 3.2 Version A, B, C. Q 3.1 Version D. Briefly describe the factors you would consider when comparing two different models. That is, how would you decide that one model was better than the other.	a) Parameter C.V.'s - too large -> smaller model b) 'U' or '/' in weighted residual versus time plot -> more parameters or larger model c) AIC - lower value better d) F-test - calculated versus tabled e) Systematic deviations on Cp versus time plot may mean a bigger model is needed
Q 3.3 Version A. Briefly describe the advantages and disadvantages of the sublingual or buccal route of drug administration.	Advantages: avoids first pass, rapid absorption, neutral pH (more stable) Disadvantages: Small dose, taste may be bad, inconvenient, advantage lost if swallowed
Q 3.3 Version B. Briefly describe the advantages and disadvantages of the intramuscular route of drug administration.	Advantages: can give larger doses or volumes (compared with SC), depot of sustained release effects possible, by-pass first pass metabolism Disadvantages: trained personal needed, site of injection affects absorption, absorption may be erratic and/or incomplete, painful, not easily reversed
Q 3.3 Version C. Briefly describe the advantages and disadvantages of the oral route of drug administration.	Advantages: convenient, portable, easy to take, cheap (relatively), compact, variety Disadvantages: sometime inefficient, low solubility and/or high dose drugs, subject to first pass effect, food interaction, GI motility effects absorption, not suitable for unconscious patient
Q 3.3 Version D. Briefly describe the advantages and disadvantages of the rectal route of drug administration.	Advantages: partially avoids first pass effect, can be given to uncoscious patients or other unable to swallow oral medication Disadvantages: erratic absorption, not well accepted
Q 3.4 Version A, B, D. Q 3.1 Version C. Briefly describe the important characteristics of subjects you may wish to use in a bioavailability study.	Age - 18 -35 yr Weight - Appropriate for height Enzyme status (smoker vs non-smoker, food or drug interaction) Number (sufficient to see effect if present) Health (healthy volunteers)