Pharmacokinetic and pharmacodynamic properties of conventional and CD-formulated diltiazem in cats.
The i.v. and apparent steady-state kinetics of diltiazem HCI (DLT) and slow-absorption long-acting diltiazem (CD) given p.o. were investigated in cats. The effects of p.o. diltiazem on heart rate and PR interval were also studied. Plasma diltiazem concentrations were determined by ultraviolet high-performance liquid chromatography (UV-HPLC), using verapamil as the internal standard. Heart rate and PR interval determinations were evaluated over a 24-hour period for the PO formulations and compared with values under diltiazemfree conditions. The mean systemic clearance and apparent volume of distribution of i.v. diltiazem were 15.0 mL/min/kg and 2.70 L/kg, respectively. The elimination half-life of diltiazem after i.v. and p.o. DLT administration were approximately 120 minutes. In contrast, the terminal half-life of CD was 460 minutes. The mean apparent bioavailability of DLT p.o. was 71%, which was significantly higher than that observed with CD (36%). Heart rate and PR intervals in cats receiving the 2 formulations at steady-state were not different from those measured in the drug-free state. We conclude that DLT at 1 mg/kg p.o. tid and CD at 10 mg/kg p.o. sid provide plasma concentrations that are known to have pharmacodynamic effects in other species.
Johnson
L M
LM
Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA.
Atkins
C E
CE
Keene
B W
BW
Bai
S A
SA
D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002415:Cats; D003692:Delayed-Action Preparations; D004110:Diltiazem / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005260:Female; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008657:Metabolic Clearance Rate
D002317:Cardiovascular Agents; D003692:Delayed-Action Preparations; D004110:Diltiazem