Symmetrical Crossover Designs for Bilateral Pharmacokinetic Drug Interactions
| Autor: | François Vandenhende, Benito J. Cerimele |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Drug
Mixed model business.industry media_common.quotation_subject Crossover Public Health Environmental and Occupational Health Estimator Pharmacology (nursing) Drug interaction Crossover study Pharmacokinetics Latin square Drug Guides Econometrics Applied mathematics Medicine Pharmacology (medical) business media_common |
| Zdroj: | Drug Information Journal. 34:411-419 |
| ISSN: | 2164-9200 0092-8615 |
| DOI: | 10.1177/009286150003400209 |
| Popis: | Bilateral pharmacokinetic interaction studies are performed to rest if the coadministration of the two drugs alters the kinetics of either one. For this purpose, standard designs are crossovers in which the two drugs are successively given alone and together Because the systemic concentration of one drug, A, will be zero when the other drug, B, is given alone and vice versa, two separate analyses for Drugs A and B are required. Two symmetrical designs which generate identical analyses for Drugs A and B are reviewed: the dual balanced two-period and the balanced Latin Square three-period designs. Their efficiency in accurately and precisely estimating direct treatment differences (AB-B) or (AB-A) is compared, when analyzed with a standard linear mixed model that either does or does not include a first-order carry-over effect. From this evaluation, the balanced three-period design is preferred because of its 25% superior efficiency when no carry-over effect is present. In the presence of carry-over; the three-period design also produces unbiased estimators for the direct treatment and carry-over effects whose variances are proportional to the within-subject variability. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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