Pharmacokinetics and relative potency assays with analgesic medications

Simulated pharmacokinetic data are used to depict how single-dose relative potency assays fail when medications with half-lives of 3, 6, 12, and 24 hours are compared. When doses are given every six hours, the steady-state maximum concentrations (as a percent of the first dose Cmax) are respectively 133, 199, 377, and 598. Conversely, the sums of the maximum and minimum concentrations following the first dose, as percent of the steady-state Cmax plus Cmin are respectively 75, 50, 30, and 17. Single-dose comparisons among usual (maintenance) doses of analgesics with different half-lives (accumulation characteristics) do not provide satisfactory estimates of relative therapeutic efficacy.