Pharmacokinetic profile of cefixime in man

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Abstract
Cefixime is an orally absorbed third generation cephalosporin with a broad spectrum of activity against Gram-positive and Gram-negative bacteria and is highly resistant to betalactamase degradation. In general serum and urinary concentrations of cefixime achieved after recommended daily doses are well above the minimal inhibitory concentrations at 90% for indicated microorganisms. The pharmacokinetics of cefixime were determined in adult and pediatric subjects. In general the half-life of the drug is about 3 to 4 hours and is not dependent on dose. The drug is not extensively bound to serum proteins; the free fraction is about 31% and is concentration-independent. The absolute bioavailability, based on comparisons of area under the serum concentration-time curve values after 200-mg intravenous, 200-mg oral solution, and 200− and 400-mg capsule doses, ranged from 40 to 52%, showing a comparable bioavailability for cefixime at single 200− and 400-mg oral doses. In a dose proportionality study, over an oral dose range of 200 to 2000 mg, peak serum concentration (Cmax) and area under the concentration-time values increased linearly but were not directly proportional with dose. Upon multiple dosing for 2 weeks on a 400-mg daily or 200-mg twice a day regimen, serum concentrations and urinary recovery of unchanged drug were similar for each group, and there was no drug accumulation. Peak serum concentration and area under the concentration-time curve values after a 400-mg dose were almost double those after a 200-mg dose. All formulations of cefixime were bioequivalent to an oral reference solution at doses of 200 and 400 mg. Because food had no effect on peak serum concentrations or the extent of drug absorption, cefixime can be taken with or without meals. Although serum concentrations were about 25% greater in elderly subjects when compared with young adults, no dosing adjustment is needed in elderly subjects. The pharmacokinetic profile of cefixime was significantly altered in patients with significant renal insufficiency (creatinine clearance [CLcr]2). There was a good relationship between CLcr and the renal clearance (Clr) of cefixime. In patients with seriously compromised renal function (CLcr2), the dose of cefixime should be reduced from 400 to 200 mg daily. Hemodialysis or peritoneal dialysis did not remove significant amounts of the drug from the body. The pharmacokinetic parameters of cefixime in pediatric patients were comparable to those measured in young and elderly adult subjects. In adults maximum serum concentrations generally range from about 3 to 5 μg/ml after a 400-mg dose and from 2 to 4 % μg/ml after a 200-mg dose. In pediatric patients a 4-mg/kg dose results in serum concentrations in the 2 to 2.5-μg/ml range, while a 6-mg/kg dose results in concentrations ranging from about 3.5 to 4 μg/ml. At a dose of 8 mg/ kg concentrations observed at 3.5 hours after the dose ranged from 2.1 to 4.8 μg/ml. Pharmacokinetic parameters in pediatric patients were similar to those observed in adults.

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