Clarithromycin has been administered to 486 subjects in 23 different Phase I studies. Absorption of clarithromycin is rapid and peak concentrations are reached within 2 h of oral dosing. Bioavailability of clarithromycin is c. 50% after oral dosing. However, additional clarithromycin is absorbed and converted into 14-OH-clarithromycin in the liver before entering the systemic circulation. The antimicrobial activity of 14-OH-(R)-clarithromycin, if anything, is superior to that of the parent compound, so that the total absorption of biologically active substance is more than 50% of the administered dose. Peak serum concentrations after oral administration of a 250 mg, film-coated tablet of clarithromycin are 1·5 mg l-1 clarithromycin and 0·8 mg l-1 of 14-OH-(R)-clarithromycin. Clarithromycin is 72% bound to plasma proteins at a concentration of 0·45 mg l-1 but binding decreases with increasing concentration of clarithromycin. Concentrations of clarithromycin in lung are approximately five-fold greater than serum concentrations. Clarithromycin is metabolized in the liver and in the stomach. Approximately 22% of an oral dose is recovered as parent compound, 18% in the urine and 4% in the faeces. Clearance of clarithromycin decreases with increasing dose, probably because of saturable hepatic metabolism. There is a progressive increase in serum concentrations of clarithromycin and 14-OH-(R)-clarithromycin with renal impairment so that doses may need to be reduced in severe impairment (glomerular filtration rate < 30 ml min-1). No effect of age on clarithromycin clearance has been demonstrated when clarithromycin clearance is corrected for creatinine clearance. Clarithromycin causes a small (24%) decrease in clearance of theophylline but this is unlikely to result in clinically significant increases in serum theophylline concentration. In conclusion, clarithromycin has enhanced, more reliable bioavailability in comparison with erythromycin but with a similar degree of tissue penetration. It offers a compromise between the extremes of roxithromycin and azithromycin. The former has high plasma concentrations but relatively low tissue concentrations whereas the very high tissue concentrations of azithromycin result in low serum concentrations. © 1991.
