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PHARMACOKINETICS AND PHARMACODYNAMICS OF 2,4‐DIAMINOPYRIDINE IN THE CAT
Author(s) -
BIESSELS P.T.M.,
HOUWERTJES M.C.,
SCAF A.H.J.,
AGOSTON S.,
HORN A.S.
Publication year - 1988
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1988.tb00647.x
Subject(s) - pharmacokinetics , volume of distribution , pharmacodynamics , cats , urine , chemistry , steady state (chemistry) , fissipedia , anesthesia , plasma concentration , pharmacology , medicine , endocrinology
Summary— 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 μg/kg IV) was administered. Plasma, urine, and bile were collected over 8 h and analyzed by means of an HPLC assay. Plasma concentrations decreased biexponen‐tially 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.