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EFFECT OF EXPERIMENTAL CHOLESTASIS ON NEUROMUSCULAR BLOCKING DRUGS IN CATS |
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| Authors: | WESTRA, P. HOUWERTJES, M. C. DE LANGE, A. R. SCAF, A. H. HINDRIKS, F. R. AGOSTON, S. |
| Affiliation: | Research Group of Anaesthesiology and Clinical Pharmacology of the Medical Faculty, State University of Groningen Bloemsingel 1, 9713 BZ Groningen, The Netherlands. Department of Pharmacology and Clinical Pharmacology, State University of Groningen Central Laboratory for Clinical Chemistry, University Hospital Groningen |
| Abstract: | Pancuronium, Org 6368 and gallamine were compared in controlcats and in cats with experimental cholestasis. A decrease inthe plasma clearance and a prolongation of neuromuscular blockadewith Org 6368 and pancuronium were found in the latter; no significantdifference was detected in the biotransformation pattern ofOrg 6368 and pancuronium compared with controls. Inhibitionof hepatic uptake of Org 6368 and pancuronium in extrahepaticcholestasis might explain the significant alterations in thepharmacokinetics of the two steroid neuromuscular blocking drugs.The pharmacokinetics of gallamine were normal during cholestasis.The results suggest that, under pathological conditions involvingincreased plasma concentrations of bile salts, neuromuscularblocking agents that are cleared from the plasma by the livermay have an impaired hepatic uptake and consequently a prolongedduration of action. |
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