Pharmacokinetics of fluphenazine, a highly lipophilic drug, estimated from a pulse dose of a stable isotopomer in dogs at steady state.
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).
Hubbard
J W
JW
College of Pharmacy & Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada, S7N 5C9. Hubbard@duke.usask.ca
Hadad
S
S
Luo
J P
JP
McKay
G
G
Midha
K K
KK
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
D014150:Antipsychotic Agents; D007202:Indicators and Reagents; D003903:Deuterium; D005476:Fluphenazine