Tergecef/Tergecef OD Mechanism of Action

Pharmacology: Pharmacodynamics: Cefixime exerts its bactericidal activity by interfering with the synthesis of the bacterial cell wall. It binds to specific penicillin-binding proteins responsible for the synthesis of peptidoglycan, a heteropolymeric structure that gives the cell wall its mechanical stability. The final stage of peptidoglycan synthesis involves completion of the cross-linking of the terminal glycine residue of the pentaglycine bridge to the fourth residue of the pentapeptide. The transpeptidase that catalyzes this step is inhibited by cephalosporins. Thus, inhibition of the transpeptidase interrupts peptidoglycan synthesis, causing formation of defective cell walls and osmotically unstable spheroplasts and lysis of the bacteria.
Pharmacokinetics: Cefixime is about 30% to 50% absorbed after oral administration; food has no effect on its absorption. Peak serum concentrations (C_max) after a single, oral 200 or 400 mg dose of cefixime as capsule, tablet or oral suspension are attained between 2 to 6 hours. Although there are differences in pharmacokinetic parameters between the formulations, results of controlled, cross-over studies in healthy adults indicate that the capsules are essentially bioequivalent to tablets. However, oral suspension is more completely absorbed than tablets, thus, tablets theoretically should not be substituted for oral suspension.
Peak serum concentrations of cefixime are approximately 15-50% higher when the drug is administered as an oral suspension rather than as tablets. When 200 and 400 mg doses of cefixime are administered as an oral suspension, peak serum concentrations average 3-3.4 mcg/mL and 4.6 mcg/mL, respectively. Areas under the concentration-time curves (AUCs) of 100-400 mg cefixime oral suspension are approximately 10-25% higher than cefixime tablets. This lack of bioequivalence between dosage forms should be considered if the oral suspension is to be substituted for tablets.
Cefixime is not extensively bound to protein; the free drug is about 31% and is concentration-dependent. The absolute bioavailability based on comparisons of the concentration-time curve values after 200 mg intravenous, 200 mg oral solution, and 200 and 400 mg capsule doses ranged from 40-52%, showing a comparable bioavailability for cefixime at single 200 and 400 mg oral doses. In a four-way cross-over study, the serum concentration time curve values of cefixime was 52.3%, 47.9%, and 40.2% after the 200 mg oral solution, 200 mg capsule and 400 mg capsule doses, respectively. Respective ratios based on 24-hour urinary recovery data were 44.7%, 41.7%, and 40.5% for the 200 mg oral solution, 200 mg capsule and 400 mg capsule doses.
The serum elimination half-life of cefixime in adults with normal renal function ranges from 2.4-4 hours. Cefixime is eliminated by renal and nonrenal mechanisms. Urinary concentrations of cefixime generally range from 2.2-103 mcg/mL during the first 2 hours and from 15.07-305 mcg/mL 6-8 hours after a single 200 or 400 mg oral dose of the drug. Fecal concentrations of cefixime in healthy adults may range from 0.237-1.55 g/kg following usual oral doses of the drug as capsules or tablets.
Studies in children using cefixime doses of 4 to 8 mg/kg body weight indicate that serum concentrations of cefixime are not directly dose proportional. In a dose proportionality study in healthy adults using an oral dose range of 200 to 2000 mg cefixime, C_max and AUC increased linearly but were not also directly proportional with dose. Upon multiple dosing for 2 weeks with a 400 mg capsule daily or 200 mg twice daily regimen, serum concentrations and urinary recovery of unchanged drug were similar for each group showing that there was no drug accumulation.
Microbiology: Antimicrobial Spectrum of Activity: Cefixime is active against the following organisms, both in vitro and in clinical infections: See Table 2.

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Cefixime has been shown to be active in vitro against most strains of Gram-positive organisms such as Streptococcus agalactiae and most strains of Gram-negative organisms such as Haemophilus parainfluenzae (β-lactamase positive and negative strains), Proteus vulgaris, Klebsiella pneumoniae, Klebsiella oxytoca, Pasteurella multocida, Providencia spp., Citrobacter amalonaticus, Citrobacter diversus, and Serratia marcescens; however, clinical efficacy has not been established.