TY - JOUR T1 - Metabolism and disposition of clarithromycin in man. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 441 LP - 446 VL - 18 IS - 4 AU - J L Ferrero AU - B A Bopp AU - K C Marsh AU - S C Quigley AU - M J Johnson AU - D J Anderson AU - J E Lamm AU - K G Tolman AU - S W Sanders AU - J H Cavanaugh Y1 - 1990/07/01 UR - http://dmd.aspetjournals.org/content/18/4/441.abstract N2 - The metabolic fate and pharmacokinetics of clarithromycin following a single 250- or 1200-mg oral dose of 14C-clarithromycin were studied in six healthy adult males. Peak plasma levels of clarithromycin averaged 0.6 microgram/ml after the low dose and 2.7 micrograms/ml after the high dose. The AUC of clarithromycin increased 13-fold, with the 4.8-fold increase in dose, while the plasma half-life increased from 4.4 hr to 11.3 hr. The major metabolite in plasma and urine was the microbiologically active 14-hydroxylated-R epimer of clarithromycin. After 5 days, a mean of 38% of the low dose (18% as clarithromycin) and 46% of the high dose (29% as clarithromycin) was recovered in the urine, with approximately one-third eliminated during the first 24 hr. The nature of the urinary and fecal metabolites revealed the involvement of three metabolic pathways, viz. 1) hydroxylation at the 14-position to form the R and S epimers, 2) N-demethylation, and 3) hydrolysis of the cladinose sugar. Secondary metabolism via these pathways was also evident. The overall recovery of metabolites, but not total radioactivity, decreased 42% after the high dose. The nonlinear pharmacokinetic behavior of clarithromycin and the decrease in metabolite production suggest that clarithromycin metabolism can be saturated at high doses. ER -