13: One Compartment PK

Why is quantitative prediction of human PK critical?

Needed to accurately project human dosage and dosing regimen for safety and efficacy of drugs

Central compartment

highly perfused organs (liver, kidneys, heart), blood

Peripheral compartment

poorly-perfused tissues (fat, muscle)

One-compartment model

(most widely used)

All tissues are combined into one well-stirred/mixed compartment; administered dose distributes instantaneously into body

Two-compartment model

similar tissues are combined into one of two compartments;

rapid distribution to central compartment then slow distribution into peripheral compartment

one compartmental Vd

volume of compartment (only one Vd for one compartment)

When does one compartmental PK apply?

When the drug distributes rapidly into its distribution volume

One compartmental Cp

concentration in compartment

One compartmental Ab

Amount of drug in the compartment is the amount of drug in the body

What kind of elimination is plasma concentration influenced by in one compartmental PK?

first-order elimination

How does plasma concentration act in IV infusions?

Gradually increases until it reaches steady state (SS after 3-5 half lives)

A

absorption dominant

B

elimination dominant

C

ONLY elimination

(for most accusation elimination rate constant, take points from this region)

IV dose one compartmental PK

first-order elimination

Oral dose one compartmental PK

first order absorption, first order elimination

Four parameters required for an oral dose in one-compartmental model

CL (elimination) & Vd (distribution)

F, ka (absorption)

What makes a larger Cmax?

if extent or rate of absorption increases