EFFECT OF DOSE SIZE ON THE PHARMACOKINETICS OF ORALLY-ADMINISTERED QUININE

Plasma concentrations of quinine were measured by high-performance liq uid chromatography (HPLC) after oral administration of 250, 500 and 10 00 mg base to seven healthy adults. The doses were administered after an overnight fast, A washout period of at least 21 days was allowed be tween the doses. Area under the plasma concentration-time curve (AUG) for quinine increased in approximate proportion to the dose from 250 t o 1000 mg, There was also a linear relationship between dose and maxim um plasma concentration and dose and AUC in individual subjects. Time to reach peak plasma concentration remained unchanged over the dose ra nge, There was no significant difference in elimination half-life, vol ume of distribution and systemic clearance over the dose range. The oc currence of adverse effects was dose and plasma quinine concentration dependent; central nervous system side effects increased as dose and p lasma concentrations increased. These data suggest that after oral adm inistration of quinine, linear pharmacokinetics occur in the dose rang e of 250-1000 mg.