title: Pharmacokinetics of fluphenazine, a highly lipophilic drug, estimated from a pulse dose of a stable isotopomer in dogs at steady state.
abstract: The potential utility of a pulse dose of a deuterium-labeled isotopomer (FLU-D(4)) in elucidating the pharmacokinetics of fluphenazine (FLU) at steady state was investigated in dogs. The single-dose oral pharmacokinetics of FLU 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. Following 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 concentrations were determined by tandem mass spectrometry. Comparable estimates of apparent 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).
authors.affiliation: College of Pharmacy & Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada, S7N 5C9. Hubbard@duke.usask.ca
authors.forename: J W
authors.initials: JW
authors.lastname: Hubbard
authors.forename: S
authors.initials: S
authors.lastname: Hadad
authors.forename: J P
authors.initials: JP
authors.lastname: Luo
authors.forename: G
authors.initials: G
authors.lastname: McKay
authors.forename: K K
authors.initials: KK
authors.lastname: Midha
mesh_terms: D000465:Algorithms; D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001711:Biotransformation; D003903:Deuterium; D004285:Dogs; D005260:Female; D005476:Fluphenazine / Q000737:chemistry / Q000493:pharmacokinetics*; D007202:Indicators and Reagents; D007536:Isomerism; D012995:Solubility
chemical_list: D014150:Antipsychotic Agents; D007202:Indicators and Reagents; D003903:Deuterium; D005476:Fluphenazine