Serum and cellular pharmacokinetics of clarithromycin 500 mg q.d. and 250 mg b.i.d. in volunteers.

In an open-label, randomized, crossover study 12 healthy volunteers were given clarithromycin orally 250 mg twice daily (b.i.d.) and 500 mg once a day (q.d.). Blood and saliva samples were collected on study days 1 and 5 to determine the pharmacokinetics of clarithromycin and its 14-hydroxy metabolite in plasma and saliva, and to measure concentrations of clarithromycin in mononuclear cells (MNCs) and polymorphonuclear leucocytes (PMNs). The mean peak levels of clarithromycin on day 5 of therapy in serum (2.3 vs. 1.2 mg/l), saliva (1.1 vs. 0.3 mg/l) and blood cells 60 vs. 26 mg/l in MNCs and 29 vs. 14 mg/l in PMNs) were at least doubled, the trough levels were lower with 500 mg q.d. vs. 250 mg b.i.d. (0.09 vs. 0.28 mg/l in serum; 0.06 vs. 0.13 mg/l in saliva; < 1 vs. 6.8 mg/l in MNCs; 0.8 vs. 2.8 mg/l in PMNs). The mean relative peak serum concentrations of the 14-hydroxy metabolite were somewhat lower with the 500 mg dosage (0.78 vs. 0.46 mg/l). The peak concentrations of clarithromycin and its 14-hydroxy metabolite in saliva were 25-40% and 50-80% of the maximum serum concentrations with both dosage regimens. Clarithromycin exhibits good and rapid penetration into intracellular as well as into extravasal extracellular body compartments. Clarithromycin 500 mg q.d. compares favourably with 250 mg b.i.d., as far as peak serum levels and bioavailability are concerned, but trough levels are lower at the end of the 24-hour dosing interval.