PHARMACOKINETIC PROFILE OF LORACARBEF (REPRINTED FROM AMERICAN JOURNAL OF MEDICINE, VOL 92, PG 165-195, 1992)

Loracarbef, the first beta-lactam antibiotic of the carbacephem class to undergo clinical evaluation, has been the subject of extensive clinical pharmacology studies. Loracarbef is well absorbed: virtually all of an orally administered dose is excreted in the urine unchanged. Following administration of a 400 mg capsule to adults twice a day for 10 days, no accumulation of drug is noted. In one study in children, following the administration of 15 mg/kg of loracarbef suspension, the mean maximum plasma concentration (C(max)) was 20.3-mu-g/mL. In adults, the C(max) following administration of the suspension or solution formulations is higher than that achieved following administration of the capsule formulation, and the time to reach peak concentration (T(max)) is increased when loracarbef is administered as a capsule; however, the area under the curve, plasma half-life, and percentage of oral dose excreted in the urine are comparable among all formulations. The ingestion of food decreases the C(max) and delays the T(max) compared with the fasting state. The pharmacokinetic profile of loracarbef in adults is comparable with that in children or the elderly. Because loracarbef is eliminated primarily by the kidney, dosage must be reduced in patients with moderate-to-severe renal insufficiency. Loracarbef achieves middle-ear and interstitial-fluid levels that generally exceed the minimum inhibitory concentrations for common bacterial pathogens. Loracarbef possesses a pharmacokinetic profile consistent with the efficacy and safety profile documented in controlled clinical trials.