THE PHARMACOKINETICS AND PHARMACODYNAMICS OF QUININE IN THE DIABETIC AND NONDIABETIC ELDERLY

1 Quinine is a front-line antimalarial drug but is prescribed most commonly in non-malarious countries for cramps. Postural hypotension, hearing loss and hyperinsulinaemic hypoglycaemia occur in malaria and overdose but little is known of quinine kinetics and toxicity in the elderly. 2 We studied 12 non-insulin-dependent diabetics and 10 non-diabetic controls aged 51-79 years. Subjects attended on two occasions >7 days apart. On each test day, subjects were given a 600 Cal meal at 18.00 h (0 h) and, on one occasion, quinine sulphate 600 mg at 22.00 h (4 h). Venous blood samples for glucose, insulin and quinine assay were drawn pre-prandially and then regularly over the next 38 h. Supine and erect blood pressures were taken and audiometry was performed at 4, 6, 8 and 14 h. A one-compartment open pharmacokinetic model was fitted to serum quinine concentrations. 3 Absorption and elimination half-times, volume of distribution and oral clearance of quinine were comparable in the two groups (P > 0.2) and there was a mean absorption lag-time of approximately 1 h. Basal and immediate post-prandial (< 4 h) serum glucose and insulin concentrations on both test days were similar in the diabetics and also in the non-diabetics, but quinine produced a mean reduction in serum glucose of 1.0 mmol 1(-1) from 3-5 h post-dose in both groups without affecting serum insulin concentrations. Quinine administration did not alter postural blood pressure changes or produce significant hearing loss in either group. 4 These data suggest that a nocturnal post-prandial dose of quinine lowers early morning plasma glucose concentrations in both non-diabetic and diabetic subjects. Other potentially significant toxic effects in elderly patients were not observed.