PHARMACOKINETIC DISPOSITION OF LORACARBEF IN HEALTHY-YOUNG MEN AND WOMEN AT STEADY-STATE

The pharmacokinetic disposition of 200- and 400-mg doses of a novel ca rbacephem, loracarbef, was determined over a dose interval on day 8, a fter ingestion of drug doses twice daily for 7 days, in 20 young, heal thy volunteers of both genders. Drug was analyzed in plasma, urine, sa liva, vaginal secretions, and fecal filtrate. Peak plasma concentratio n was proportional to dose for both men (4.0 +/- 1.3 and 8.8 +/- 3.4 m g/L) and women (8.0 +/- 5.6 and 15.3 +/- 3.3 mg/L), and the observed t ime to peak increased from 1 to 2 hours with the increased dose. Appar ent volume of distribution was greater in men than women (0.385 +/- 0. 114 versus 0.270 +/- 0.075 L/kg; P <.03). The drug was virtually quant itatively excreted unchanged in urine, and its renal clearance exceede d creatinine clearance in all subjects. Renal loracarbef clearance cor related with neither weight-corrected dose nor creatinine clearance in these healthy subjects. There was no evidence for drug accumulation i n the body with chronic ingestion. Loracarbef was detected in the feca l filtrate of seven volunteers, but did not account for more than 7% o f the daily dose. Loracarbef was detected in vaginal secretions of two of five volunteers who ingested the 400-mg dose. No drug was detected in saliva obtained lust before dose ingestion. These data are consist ent with complete bioavailability for an oral beta-lactam antibiotic d rug that is virtually completely eliminated unchanged by the kidney.