The statistical evaluation of a three-period two-treatment crossover pharmacokinetic drug interaction study
J L Ciminera1, J A Bolognese, M H Gregg
1Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.
Abstract:
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.
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