Pharmacology: Clarithromycin is a semisynthetic macrolide antibiotic with activity against many gram-positive and gram-negative aerobic and anaerobic organisms. Clarithromycin usually is bacteriostatic, although it may be bactericidal in high concentrations or against highly susceptible organisms such as S. pyogenes, S. pneumoniae, H. influenzae and Chlamydia trachomatis. Clarithromycin inhibits protein synthesis in susceptible organisms by penetrating the cell wall and binding to 50S ribosomal subunits, thereby inhibiting translocation of aminoacyl transfer-RNA and inhibiting polypeptide synthesis. Clarithromycin is absorbed rapidly from the GI tract after oral administration with an absolute bioavailability of approximately 50-55%. Food delays the rate, but not the extent of absorption. The drug undergoes extensive first-pass metabolism. Clarithromycin and its active metabolite are widely distributed into most body tissues and fluid except the CSF. Concentrations in tissues are higher than in serum. It is 42-72% bound to plasma protein. Clarithromycin is metabolized in the liver, prinicipally by oxidative N-demethylation, hydroxylation, and hydrolysis to metabolites. One metabolite, 14-hydroxyclarithromycin, has antimicrobial activity comparable to clarithromycin and may act synergistically with the drug against H. influenzae. The elimination half-life of clarithromycin are 3-4 hours and 5-7 hours following 250 and 500 mg dose; the half-life of 14-hydroxyclarithromycin are 5-6 hours with 250 mg dose and 7-9 hours with 500 mg dose. Approx, 20 and 30%, respectively, of the dose of 250 and 500 mg tablets given every 12 hours is excreted unchanged in urine within 12 hours. The principal metabolite, 14-hydroxyclarithromycin, which accounts for approx. 10-15% of the dose is excreted in urine after a 250 and 500 mg dose every 12 hours.
The serum half-life of clarithromycin is prolonged in patients with impaired renal function. The reduction of clarithromycin dosage may be required if creatinine clearance is less than 30 mL/min.