PHAR 7633 Fall 1999

Pharmacokinetics

OU HSC College of Pharmacy

Second Exam 12 November 1999

Section THREE. Short Answer 3 x 5 = 15 points

Remember to limit the time spent on this section.


Q3.1 Version A. Briefly describe how a drug concentration plateau is achieved after multiple IV doses.

When elimination follows first order kinetics the amount or rate of drug removed is proportional the amount in the body. Thus as more dose are given and the amount in the body increases the amount eliminated increases as well. Thus, at some point the amount elimination during a dosing interval is the same as the dose. From this point Cpmin and Cpmax concentrations remain constant as long as the dosing regimen is maintained.

Q3.2 Version A. Briefly describe the parameter Cp(bar), providing a definition, an equation suitable for estimating this parameter, and units.

The parameter C(bar) represents the average plasma concentration during a dosing interval. If could be defined as the area under the concentration time curve during the interval divided by the interval duration or AUC/tau. Units are those of concentration, i.e. mg/L. Another useful equations might be Cp(bar) = F*Dose/(V*kel*tau), where tau is the dosing interval.

Q3.3 Version C. Briefly describe the parameter Cpmin, providing a definition, an equation suitable for estimating this parameter, and units.

Cpmin is the minimum concentration achieved during multiple dose administration. Units are those of concentration, i.e. mg/L. After many uniform IV bolus doses and after uniform dosing intervals, Cpmin can be calculated as (Dose/V)*(R/(1 - R)) where R is e-kel*tau where tau is the dosing interval.

Q3.1 Version D. Briefly describe the parameter, t (or tau) , providing a definition, an equation suitable for estimating this parameter, and units.

Tau is used to represent the dosing interval during multiple dose drug administration. The units are those of time, e.g. hr. A desired tau can be calculated from Cpmin and Cpmax if you know kel. tau = ln(Cpmax/Cpmin)/kel (derived from R = e-kel*tau = Cpmin/Cpmax)

Q3.2 Version B. Briefly describe the term, R, as it is used in the area of multiple dose drug administration. Include a definition, a useful (working equation), and units.

R is used to represent the fraction of drug remaining at the end of a dosing interval. Since it is a ratio it has no units. R can be calculated as e-kel*tau = Cpmin/Cpmax

Q3.3 Version A. Q3.2 Version D. Briefly describe the superposition principle.

If drug disposition (distribution, elimination, and metabolism) is first order or linear the superposition principle can be used to calculate drug concentrations after uniform and nonuniform dosing regimens. To use this method one calculates the concentration from each dose separately and adds these values together to determine the total concentration due to the dosing regimen.

Q3.1 Version B. Briefly describe the term induction as it relates to drug metabolism.

Most drug metabolism processes involve enzyme reactions. Certain compounds such as some drugs, chemicals ingested after smoking or after grilled food may cause an increase or 'induce' and increase in enzyme capability. Thus after induction the metabolism of a drug may be faster. This induction process may take a few days to reach its maximum effect.

Q3.3 Version D. Briefly describe the term inhibition as it relates to drug metabolism.

Most drug metabolism processes involve enzyme reactions. Frequently the same enzyme may be responsible for the metabolism of more than one drug or compound. Thus, one drug may compete with the metabolism of another, that is, it may inhibit the metabolism of the second drug. Thus, the drug metabolism may be reduced through inhibition by another drug or compound.

Q3.3 Version B. Briefly describe the types of reactions involved in Phase I metabolism.

These reactions include oxidation, reduction, and hydrolysis. Oxidation is the addition of oxygen or removal of a hydrogen atom. Examples might include formation of alcohols or phenols. Reduction is the removal of oxygen or addition of hydrogen. Examples include the reduction of a nitro to amine group. Hydrolysis is the addition of water to a molecule usually resulting in the subsequent breakdown of the molecule. Examples might include the hydrolysis of esters and amides.

Q3.1 Version C. Briefly describe enterohepatic recycling.

Drugs are extensively excreted into bile may be subject to enterohepatic recycling. Typically these include larger molecules of about 500 Dalton and may include molecules that might be metabolized by conjugation (which results in a larger molecule). In humans these drugs are stored in the gall bladder. The gall bladder is often periodically emptied in response to a stimulus such as food. The drug may then be reabsorbed to create a second peak in the concentration time curve.

A sketch illustrating enterohepatic recycling. A figure illustrating what can happen when a drug is subject to enterohepatic recycling.

Q3.2 Version C. Briefly describe the processes involved in drug excretion that occur in the nephron.

There are four regions of interest. i) The glomerular where drugs and other small compounds are filtered from the blood/plasma; ii) In the proximal tubule there may be (active) secretion of acidic drugs and some reabsorption of water; iii) In the Loop of Henle there is reabsorption of water; and iv) In the distal tubule there is passive reabsorption of lipid soluble drugs (or forms of the drug) and more water.


This file was last modified: Wednesday 26 May 2010 at 07:21 PM
Copyright 1999 David W.A. Bourne