Loracarbef, after oral administration, was approximately 90% absorbed from the gastrointestinal tract. When capsules were taken with food, peak plasma concentrations were 50% to 60% of those achieved when the drug was administered to fasting subjects and occurred from 30 to 60 minutes later. Total absorption, as measured by urinary recovery and area under the plasma concentration versus time curve (AUC), was unchanged. The effect of food on the rate and extent of absorption of the suspension formulation has not been studied to date.

The pharmacokinetics of loracarbef were linear over the recommended dosage range of 200 to 400 mg, with no accumulation of the drug noted when it was given twice daily.

Average peak plasma concentrations after administration of 200-mg or 400-mg single doses of loracarbef as capsules to fasting subjects were approximately 8 to 14 mcg/ml, respectively, and were obtained within 1.2 hours after dosing. The average peak plasma concentration in adults following a 400-mg single dose of suspension was 17 mcg/ml and was obtained within 0.8 hour after dosing (see TABLE 1).

Following administration of 7.5 and 15 mg/kg single doses of oral suspension to children, average peak plasma concentrations were 13 and 19 mcg/ml, respectively, and were obtained within 40 to 60 minutes.

This increased rate of absorption (suspension > capsule) should be taken into consideration if the oral suspension is to be substituted for the capsule, and capsules should not be substituted for the oral suspension in the treatment of otitis media (see DOSAGE AND ADMINISTRATION).

The elimination half-life was an average of 1.0 h in patients with normal renal function. Concomitant administration of probenecid decreased the rate of urinary excretion and increased the half-life to 1.5 hours.

In subjects with moderate impairment of renal function (creatinine clearance 10 to 50 ml/min/1.73 m²), following a single 400-mg dose, the plasma half-life was prolonged to approximately 5.6 hours. In subjects with severe renal impairment (creatinine clearance <10 ml/min/1.73 m²), the half-life was increased to approximately 32 hours. During hemodialysis the half-life was approximately 4 hours. In patients with severe renal impairment, the C_max increased from 15.4 mcg/ml to 23 mcg/ml (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).

In single-dose studies, plasma half-life and AUC were not significantly altered in healthy elderly subjects with normal renal function.

There is no evidence of metabolism of loracarbef in humans.

Approximately 25% of circulating loracarbef is bound to plasma proteins.

Middle-ear fluid concentrations of loracarbef were approximately 48% of the plasma concentration 2 hours after drug administration in pediatric patients. The peak concentration of loracarbef in blister fluid was approximately half that obtained in plasma. Adequate data on CSF levels of loracarbef are not available.

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