Pharmacokinetics and metabolism of diltiazem in rabbits after a single intravenous or single oral administration.
Diltiazem (DTZ) 5 mg/kg was given to rabbits either orally (n = 5) or intravenously (n = 6). Plasma concentrations and urinary excretion of DTZ and its metabolites were determined by a high performance liquid chromatography assay (HPLC) for 12 and 48 h post dose, respectively. The results showed that the metabolism and disposition of DTZ in rabbits was similar to that of humans, mean absolute bioavailability (F) of DTZ was approximately 30% and the systemic clearance was 64.0 ml/min/kg. The metabolism of DTZ between the two routes of administration was quantitatively different in that higher plasma concentrations of the metabolites were observed after the intravenous dose. This could be a result of incomplete oral absorption, higher clearance of DTZ and the metabolites during the first pass through the liver (i.e. higher sequential first pass effect), and/or extrahepatic metabolism. On the basis of the plasma concentration-time profiles and urinary excretion of DTZ and its metabolites, it is concluded that the rabbit is a suitable animal model to investigate the kinetics and metabolism of DTZ.
Yeung
P K
PK
College of Pharmacy, Faculty of Health Professions, Dalhousie University, Halifax, Nova Scotia, Canada.
Mosher
S J
SJ
Pollak
P T
PT
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004110:Diltiazem / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D007700:Kinetics; D011817:Rabbits
D004110:Diltiazem