Pharmacokinetics of fluphenazine, a highly lipophilic drug, estimated froma pulse dose of a stable isotopomer in dogs at steady state

The potential utility of a pulse dose of a deuterium-labeled isotopomer (FL U-D-4) in elucidating the pharmacokinetics of fluphenazine (FLU) at Steady state was investigated in dogs. The single-dose oral pharmacokinetics of FL U in dogs were established. After resting the dogs for 3 weeks, the animals were dosed to steady state with oral FLU administered at 12-h intervals. F ollowing 15 doses, one dose of FLU was replaced by a pulse dose of FLU-D-4, after which dosing with FLU was resumed. FLU and FLU-D-4 plasma concentrat ions were determined by tandem mass spectrometry. Comparable estimates of a pparent oral clearance were calculated from (i) a single dose of FLU, (ii) a pulse dose of FLU-D-4, and (iii) over a dosing interval at steady state. Average steady-state plasma concentrations were reliably predictable from a pulse dose of FLU-D-4.