alexa Clarithromycin clinical pharmacokinetics.
Chemistry

Chemistry

Pharmaceutical Analytical Chemistry: Open Access

Author(s): Fraschini F, Scaglione F, Demartini G

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Abstract 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. This article was published in Clin Pharmacokinet and referenced in Pharmaceutical Analytical Chemistry: Open Access

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