The concentrations of clarithromycin and its active principal metabolite, 14-(R)-hydroxy-clarithromycin were determined in lung tissue obtained during lung resection and compared with concomitant concentrtions in plasma. Concentrations of the parent and metabolite were determined by high-perfoien l chromatography. The 15 patients studied were given 500 mg orally every 12 h for a minimum of five do4 to achieve steady-state concentrations. The mean concentrations of clarithromycin and 14-(R)-hydryayllwomycin in plasma just prior to the final dose were 1.38 and 0.67 p,g/ml, respectively, and those 4 h after the final dose (at the time of lung resection) were 1.89 and 0.80 ,ug/mL, respectively. The concentrations of the parent and metabolite in lung tissue at the time of lung resection averaged 54.3 and 5.12 ,ug/g, respectively, with a mean calculated ratio of concentrations of the parent to metabolite being 11.3 in lung tissue and 2.4 in plasma. Clarithromycin and its active metabolite are extensively distributed into human lung tissue.

A 42-year-old man who had received a cadaveric kidney transplant 9 years earlier was admitted to the hospital with pneumonia. His oral cyclosporine dosage for the past 2 years was stabilized at 100 mg twice/day; his cyclosporine whole blood trough levels 15 days earlier and on the day he was admitted were both 178 ng/ml. The patient was treated with intravenous ceftriaxone and intravenous azithromycin and continued to receive the same dosage of oral cyclosporine. On hospital day 3, his cyclosporine trough level rose to 400 ng/ml and his dosage was reduced by 50%. Trough levels were 181 ng/ml and 175 ng/ml on hospital days 6 and 9, respectively On hospital day 9, the patient stopped receiving azithromycin. On hospital day 14, his cyclosporine trough level dropped to 76 ng/ml, and his cyclosporine dosage was increased back to 100 mg twice/day. The dosage produced trough levels consistent with those before he had been admitted. The patient was discharged on day 20, and a follow-up cyclosporine trough level determined 3 weeks later was 175 ng/ml. Administration of azithromycin may have caused the increased cyclosporine concentrations in this patient through p-glycoprotein inhibition and/or competition for biliary excretion. Azithromycin's interference may be inferred by the increase in cyclosporine levels after administration of this drug and the decrease in cyclosporine levels after its discontinuation-both consistent with the pharmacokinetic properties of cyclosporine. Ceftriaxone and acute-phase reactant activation during infection, however, also may have interfered with the patient's cyclosporine elimination. Azithromycin generally is considered unlikely to interact with cyclosporine. Nonetheless, practitioners should be aware of this possibility and should monitor cyclosporine levels closely, especially in critically ill patients who have other complications.

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