Guidelines for selecting multiple-dose/multiple-dose design trials
Multiple-Dose/Multiple-Dose Design Conditions |
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| 1. Specific safety issues are possible that depend on achieving steady-state exposure of both compounds. |
| 2. The interaction is not strictly competitive, e.g., mechanism-based or suicidal inhibition occurs or may occur. |
| 3. A claim that widens the absolute bioequivalency criteria is desired. |
| 4. The time course of induction or inhibition needs to be determined. |
| 5. First dose effects require titration to a standard steady-state dose for either compound. |
| 6. One drug shows a significant accumulation ratio and a single-dose regimen that achieves comparable steady-state concentrations is not feasible. |
| 7. One of the drugs at steady-state concentrations forms a metabolite that produces additive induction or inhibition, which cannot be demonstrated through the administration of larger single doses. |
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8. Dose-dependent or time-dependent pharmacokinetics, e.g., phenytoin or
omeprazole, respectively, leading to at least a 50 to 100% accumulation of
parent.
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