Tubocurarine and renal failure

Different observations concerning the duration of the neuromuscular blocking effect of tubocurarine in patients with renal failure have been rationalized by pharmacokinetic analysis. Computer simulations predict that absence of renal function will have little effect on the duration of action of relatively small single doses of tubocurarine but that the duration of action of large single doses and multiple doses will be prolonged significantly. It is now generally recognized that renal failure or impaired renal function requires changes in the dosage regimen of many drugs to prevent drug accumulation and toxic effects (Bennett, Singer and Coggins, 1970). A rigorous pharmacokinetic approach for calculating individualized dosage regimens of rapidly distributed drugs for patients with impaired renal function has been presented recently (Dettli, 1970). Considerably more complicated are assess-ments of the likely effect of renal failure on the elimination kinetics and particularly on the pharmacological effect of drugs with so-called multiple-compartment distribution characteristics. The time course of action of such drugs (of which tubocurarine is one) depends on the site of action of the drug; more specifically, on the apparent body compartment of which the site of action is a part (Gibaldi, Levy and Weintraub, 1971). It has been shown recently that the kinetics of the neuromuscular blocking effect of tubocurarine in man can be characterized effectively and rigorously on the basis of a three-compartment linear system for tubocurarine distribution and elimination, with the site of action located in the central compartment (Gibaldi, Levy and Hayton, 1972). This permits an assessment of the likely effect of renal failure on the duration of action of tubocurarine under different dosing conditions. Such an assessment is deemed particularly timely and pertinent in view of recent observations on the effect of renal failure on the duration of the neuromuscular blocking effect of tubocurarine. Riordan and Gilbertson (1971) described a patient with chronic renal failure wh