Pharmacokinetics of d-tubocurarine in man: effect of an osmotic diuretic on urinary excretion.

Abstract

The pharmacokinetics of d-tubocurarine (dTc) and the urinary excretion of dTc were studied in 18 neurosurgical patients with normal renal function, over a period of 96 hours. The effects of an osmotic diuretic (mannitol) on urinary elimination of dTc were determined. Following a single intravenous dose of d-tubocurarine (dTc, 0.3 mg/kg), serum levels and urinary excretion of the drug were measured. A specific radioimmunoassay was used for the analysis of dTc. Nine of the patients also received mannitol, 1 g/kg, after the injection of dTc for surgical indications. The study showed that only 45 per cent of the injected dose of dTc was excreted in 24 hours. Between 24 and 96 hours, an additional 7 per cent of the drug was excreted in the urine. The administration of mannitol, an osmotic diuretic, did not increase the excretion of dTc. The time-concentration relationship of serum concentration of dTc was analyzed. Using the four-exponential equation (data to 96 hours), the calculated volume of distribution (Vdarea) was 3.4 1/kg. This volume, which is greater than the volume of total body water, suggests that dTc is stored in certain tissues in the body and slowly released over a period of days to weeks.