The pharmacokinetics and pharmacodynamics of quinine in the diabetic and non-diabetic elderly.
1. Quinine is a front-line antimalarial drug but is prescribed most commonly in nonmalarious 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 l-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Dyer
J R
JR
University of Western Australia, Department of Medicine, Fremantle Hospital, Western Australia.
Davis
T M
TM
Giele
C
C
Annus
T
T
Garcia-Webb
P
P
Robson
J
J
D000042:Absorption; D000284:Administration, Oral; D000368:Aged; D000704:Analysis of Variance; D001299:Audiometry; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003198:Computer Simulation; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D034381:Hearing Loss / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007003:Hypoglycemia / Q000139:chemically induced; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D011803:Quinine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
D001786:Blood Glucose; D007328:Insulin; D011803:Quinine