Pharmacokinetics of d-Tubocurarine in Man

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Abstract
The pharmacokinetics of d-tubocurarine (dTc) and the urinary excretion of dTc were studied in 18 neurosurgical patients with normal renal function, over 96 h. The effects of an osmotic diuretic (mannitol; MT) on urinary elimination of dTc were determined. Following a single 0.3 mg/kg i.v. dose of dTc, serum levels and urinary excretion of the drug were measured. A specific radioimmunoassay was used for the analysis of dTc. Of the patients, 9 also received MT, 1 g/kg, after the injection of dTc for surgical indications. The study showed that only 45% of the injected dose of dTc was excreted in 24 h. Between 24 and 96 h, an additional 7% of the drug was excreted in the urine. The administration of MT, an osmotic diuretic, did not increase the excretion of dTc. The time-concentration relationship of serum concentration of dTc was analyzed. Using the 4 exponential equation (data to 96 h), the calculated volume of distribution was 3.4 l/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 days to weeks.