The statistical evaluation of a three-period two-treatment crossover pharmacokinetic drug interaction study.
In a pharmacokinetic drug interaction study, the purpose is to determine whether the coadministration of a drug A with a second drug B alters the absorption/distribution/metabolism/elimination profile of either drug. While the usual design for such studies is a three-period crossover, it cannot be analyzed as such, because the plasma-level data of drug B will be 0 when drug A is given alone, and vice versa. The easiest way to proceed is to do two sets of paired analyses, one on the absorption profile of A (A vs AB), and the other on the absorption profile of B (B vs AB). A complete separation of the total sources of variation and degrees of freedom is presented along with a numerical example.
Ciminera
J L
JL
Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.
Bolognese
J A
JA
Gregg
M H
MH
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000378:metabolism; D004077:Digoxin / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004656:Enalapril / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D017706:Lisinopril; D008433:Mathematics
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D004077:Digoxin; D017706:Lisinopril