SERUM AND CELLULAR PHARMACOKINETICS OF CLARITHROMYCIN 500 MG QD AND 250 MG BID IN VOLUNTEERS

In an open-label, randomized, crossover study 12 healthy volunteers we re 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 da ys 1 and 5 to determine the pharmacokinetics of clarithromycin and its 14-hydroxy metabolite in plasma and saliva, and to measure concentrat ions of clarithromycin in mononuclear cells (MNCs) and polymorphonucle ar 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 p eak serum concentrations of the 14-hydroxy metabolite were somewhat lo wer with the 500 mg dosage (0.78 vs, 0.46 mg/l). The peak concentratio ns of clarithromycin and its 14-hydroxy metabolite in saliva were 25-4 0% and 50-80% of the maximum serum concentrations with both dosage reg imens, Clarithromycin exhibits good and rapid penetration into intrace llular as well as into extravasal extracellular body compartments, Cla rithromycin 500 mg q.d. compares favourably with 250 mg b.i.d., as far as peak serum levels and bioavailability are concerned, but trough le vels are lower at the end of the 24-hour dosing interval.