CLARITHROMYCIN CLINICAL PHARMACOKINETICS

Clarithromycin is a semisynthetic macrolide antibiotic, structurally r elated to erythromycin. It has a more favourable pharmacokinetic profi le than erythromycin, thus allowing twice-daily administration and pos sibly increasing compliance among outpatients. Clarithromycin is well absorbed from the gastrointestinal tract and its systemic bioavailabil ity (about 55%) is reduced because of first-pass metabolism. It underg oes rapid biodegradation to produce the microbiologically active 14-hy droxy-(R)-metabolite. The maximum serum concentrations of clarithromyc in and its 14-hydroxy metabolite, following single oral doses, are dos e proportional and appear within 3 hours. With multiple doses, steady- state concentrations are attained after 5 doses and the maximal serum concentrations of clarithromycin and of the 14-hydroxy derivative appe ar within 2 hours after the last dose. Clarithromycin is well distribu ted throughout the body and achieves higher concentrations in tissues than in the blood. Also, the 14-hydroxy metabolite exhibits high tissu e concentrations, with values about one-third of the parent compound c oncentrations. The presence of food appears to have no clinically sign ificant effect on clarithromycin pharmacokinetics. The main metabolic pathways are oxidative N-demethylation and hydroxylation, which are sa turable and result in nonlinear pharmacokinetics. The primary metaboli te (14-hydroxy derivative) is mainly excreted in the urine with the pa rent compound. A reduction in urinary clearance in the elderly and in patients with renal impairment is associated with an increase in area under the plasma concentration-time curve, peak plasma concentrations and elimination half-life. Mild hepatic impairment does not significan tly modify clarithromycin pharmacokinetics. In conclusion, clarithromy cin, because of its antibacterial activity and pharmacokinetic propert ies, appears to be a useful alternative to other macrolides in the tre atment of community acquired infections.