Clarithromycin clinical pharmacokinetics.
Clarithromycin is a semisynthetic macrolide antibiotic, structurally related to erythromycin. It has a more favourable pharmacokinetic profile than erythromycin, thus allowing twice-daily administration and possibly increasing compliance among outpatients. Clarithromycin is well absorbed from the gastrointestinal tract and its systemic bioavailability (about 55%) is reduced because of first-pass metabolism. It undergoes rapid biodegradation to produce the microbiologically active 14-hydroxy-(R)-metabolite. The maximum serum concentrations of clarithromycin and its 14-hydroxy metabolite, following single oral doses, are dose 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 appear within 2 hours after the last dose. Clarithromycin is well distributed throughout the body and achieves higher concentrations in tissues than in the blood. Also, the 14-hydroxy metabolite exhibits high tissue concentrations, with values about one-third of the parent compound concentrations. The presence of food appears to have no clinically significant effect on clarithromycin pharmacokinetics. The main metabolic pathways are oxidative N-demethylation and hydroxylation, which are saturable and result in nonlinear pharmacokinetics. The primary metabolite (14-hydroxy derivative) is mainly excreted in the urine with the parent 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 significantly modify clarithromycin pharmacokinetics. In conclusion, clarithromycin, because of its antibacterial activity and pharmacokinetic properties, appears to be a useful alternative to other macrolides in the treatment of community acquired infections.
Fraschini
F
F
Department of Pharmacology, University of Milan, Italy.
Scaglione
F
F
Demartini
G
G
D000042:Absorption; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001424:Bacterial Infections / Q000188:drug therapy; D001682:Biological Availability; D002648:Child; D017291:Clarithromycin / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D004347:Drug Interactions; D004361:Drug Tolerance; D006801:Humans; D008875:Middle Aged
D017291:Clarithromycin