Pharmacokinetic Disposition of Loracarbef in Healthy Young Men and Women at Steady State

Abstract

The pharmacokinetic disposition of 200- and 400-mg doses of a novel carbacephem, loracarbef, was determined over a dose interval on day 8, after ingestion of drug doses twice daily for 7 days, in 20 young, healthy volunteers of both genders. Drug was analyzed in plasma, urine, saliva, vaginal secretions, and fecal filtrate. Peak plasma concentration was proportional to dose for both men (4.0 +/- 1.3 and 8.8 +/- 3.4 mg/L) and women (8.0 +/- 5.6 and 15.3 +/- 3.3 mg/L), and the observed time to peak increased from 1 to 2 hours with the increased dose. Apparent 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 quantitatively excreted unchanged in urine, and its renal clearance exceeded creatinine clearance in all subjects. Renal loracarbef clearance correlated with neither weight-corrected dose nor creatinine clearance in these healthy subjects. There was no evidence for drug accumulation in the body with chronic ingestion. Loracarbef was detected in the fecal filtrate of seven volunteers, but did not account for more than 7% of 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 just before dose ingestion. These data are consistent with complete bioavailability for an oral beta-lactam antibiotic drug that is virtually completely eliminated unchanged by the kidney.

Multiple Pharmacokinetic Parameter Prediction for a Series of Cephalosporins

“…The PK parameters of a series of 20 cephalosporins were collected from the literature,11–32 and compounds were divided into working (training and testing) and validation subsets (Table 1). Data for all compounds were taken from studies using intravenous administration of the drug, with the exception of cefaclor.…”