Pharmacokinetics and pharmacodynamics of 2,4-diaminopyridine in the cat.
The pharmacokinetics, antagonistic effects, and cardiovascular effects of 2,4-diaminopyridine (2,4-DAP) were studied in 7 anaesthetized cats. Cats received a pancuronium infusion at a constant rate to cause a 90% block of contraction of the anterior tibialis muscle, stimulated through the sciatic nerve. After steady state was reached, 2,4-DAP (750 micrograms/kg IV) was administered. Plasma, urine, and bile were collected over 8 h and analyzed by means of an HPLC assay. Plasma concentrations decreased biexponentially with half-lives of 9.0 +/- 5.7 min and 140 +/- 36 min, respectively. The volume of the central compartment was 0.85 +/- 0.27 L/kg, and the volume of distribution in the steady state was 3.1 +/- 1.1 L/kg. Total plasma clearance was 18 +/- 5 ml/kg/min. Ninety percent of the administered dose was recovered in the urine and 0.1 percent in the bile in 8 h. The antagonism of the pancuronium-induced steady-state block was 98% +/- 5%, with onset and duration of 3.5 +/- 2 min and 165 +/- 40 min, respectively.
Biessels
P T
PT
Department of Pharmacology/Clinical Pharmacology, University of Groningen, The Netherlands.
Houwertjes
M C
MC
Scaf
A H
AH
Agoston
S
S
Horn
A S
AS
D015761:4-Aminopyridine / Q000031:analogs & derivatives*; D000631:Aminopyridines / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D001711:Biotransformation; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D006339:Heart Rate / Q000187:drug effects
D000631:Aminopyridines; C026805:2,4-diaminopyridine; D015761:4-Aminopyridine