ABSTRACT
The concentrations of 4-aminopyridine hydrochloride in the blood and urine from volunteers were measured following a bolus injection i.v. of 0.3 mg kg-1. The drug was assayed by means of a new GLC method which is described. The pharmacokinetics of 4-aminopyridine are complicated by an additional increase in plasma concentration during the elimination phase of the drug.
Subject(s)
Aminopyridines/metabolism , 4-Aminopyridine , Adult , Chromatography, Gas/methods , Humans , Kinetics , Time FactorsABSTRACT
The plasma clearance of pancuronium in patients with extrahepatic cholestasis was 16% lower than in a control group (1.47 +/- 0.11 ml min-1 kg-1 v. 1.76 +/- 0.21 ml min-1 kg-1), but the difference was not significant. A significant increase in the elimination half-life T 1/2 beta of pancuronium (from 141 to 224 min) and a significant increase in the volume of the peripheral compartment (V2) was found in patients with extrahepatic cholestasis when compared with control patients. There was a significantly lower cumulative biliary excretion of pancuronium (0.3 +/- 0.3% v. 10.9 +/- 3.2% in the controls) during the 48-h period of observation. The biotransformation and cumulative urinary excretion patterns of pancuronium revealed no significant differences between the two groups of patients. The increase of T 1/2 beta pancuronium in patients with extrahepatic cholestasis was mainly a consequence of the increase in the volume of distribution. No significant differences in the plasma clearance, T 1/2 beta or in the volume of distribution were observed with gallamine in the patients with extrahepatic cholestasis when compared with the control group. The cumulative urinary excretion of gallamine during 48 h in both groups of patients was approximately 100%. We concluded that in patients with cholestasis and normal glomerular filtration, gallamine is probably more reliable than pancuronium for neuromuscular blockade.
Subject(s)
Cholestasis, Extrahepatic/metabolism , Gallamine Triethiodide/metabolism , Pancuronium/metabolism , Adult , Aged , Bile/metabolism , Biotransformation , Female , Gallamine Triethiodide/pharmacology , Half-Life , Humans , Kidney/metabolism , Kinetics , Liver/metabolism , Male , Metabolic Clearance Rate , Middle Aged , Neuromuscular Junction/drug effects , Pancuronium/pharmacologyABSTRACT
Pancuronium, Org 6368 and gallamine were compared in control cats and in cats with experimental cholestasis. A decrease in the plasma clearance and a prolongation of neuromuscular blockade with Org 6368 and pancuronium were found in the latter; no significant difference was detected in the biotransformation pattern of Org 6368 and pancuronium compared with controls. Inhibition of hepatic uptake of Org 6368 and pancuronium in extrahepatic cholestasis might explain the significant alterations in the pharmacokinetics of the two steroid neuromuscular blocking drugs. The pharmacokinetics of gallamine were normal during cholestasis. The results suggest that, under pathological conditions involving increased plasma concentrations of bile salts, neuromuscular blocking agents that are cleared from the plasma by the liver may have an impaired hepatic uptake and consequently a prolonged duration of action.
