Refix Mechanism of Action

Pharmacology: Pharmacodynamics: Capsule: Cefixime is a third generation cephalosporin with antibacterial activity similar to penicillins, carbacephems and cephamycins.
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 formulation of defective cell walls and osmotically unstable spheroplasts and lysis of the bacteria.
Pharmacokinetics: Capsule: About 30% to 50% of a single oral dose of cefixime is absorbed. Food decreases the rate but generally does not affect the extent of drug 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 about 15 to 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 to 3.4 mcg/mL and 4.6 mcg/mL, respectively. Areas under the concentration-time curves (AUCs) of 100 to 400 mg cefixime oral suspension are approximately 10 to 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.
When cefixime oral suspension at a single dose of 4, 6, or 8 mg per kg body weight was administered to children 6 months to 6 years old or older, mean serum concentrations (C_max) attained to 3.5 to 4.5 hours after the dose were 2.18 to 2.44, 3.55 to 4.07, and 3.4 to 3.91 mcg/mL, respectively. Serum concentrations of cefixime are not directly dose proportional at doses of 4 to 8 mg/kg body weight in children. Little or no accumulation of cefixime occurs after multiple dosing.
After oral administration, cefixime is distributed into bile, sputum, tonsils, maxillary sinus mucosa, middle ear discharge, blister fluid, and prostatic fluid. Sputum concentrations may be 2% to 10% of concurrent serum concentrations; in one study, a single 200 mg oral dose of cefixime resulted in sputum concentrations of 0.03 to 0.12 mcg/mL. It is not known whether cefixime is distributed into CSF after oral administration.
About 65% to 75% of cefixime is bound to serum proteins, principally albumin, and such binding is not concentration-dependent over the range of 0.5 to 30 mcg/mL. The fraction of free cefixime in plasma may be slightly greater in patients with renal impairment than in those with normal renal function.
Cefixime crosses the placenta and is distributed in low concentrations into amniotic fluid and cord serum; cord serum concentrations may be 15% to 50% of concurrent maternal plasma concentrations. No data are available on secretion of cefixime into human milk.
The half-life of cefixime is about 3 to 4 hours is not dose-dependent. It is excreted renally via glomerular filtration and to a lesser extent by tubular secretion. Metabolites of cefixime have not been isolated from human serum or urine. About 7% to 41% of a single oral dose of the drug is excreted unchanged in urine within 24 hours. The remainder of the dose (up to 60%) is eliminated by nonrenal mechanism. In animal studies, it was noted that up to 10% of a single oral dose of cefixime is excreted unchanged in bile.
Cefixime is not removed to a significant degree by either hemodialysis or peritoneal dialysis.
Granules for oral suspension: Only 40% to 50% of an oral dose of cefixime is absorbed from the gastrointestinal tract, whether taken before or after meals, although the rate of absorption may be decreased in the presence of food. Cefixime is better absorbed from oral suspension than from tablets. Absorption is fairly slow. Peak plasma concentrations of 2 to 3 μg per mL and 3.7 to 4.6 μg per mL have been reported between 2 and 6 hours after single doses of 200 and 400 mg, respectively. The plasma half-life is usually about 3 to 4 hours and may be prolonged when there is renal impairment. About 65% of cefixime in the circulation is bound to plasma proteins. Information on the distribution of cefixime in body tissues and fluids is limited. It crosses the placenta. Relatively high concentrations may be achieved in bile and urine. About 20% of an oral dose (or 50% of an absorbed dose) is excreted unchanged in the urine within 24 hours. Up to 60% may be eliminated by non renal mechanisms; there is no evidence of metabolism but some is probably excreted into the faeces from bile. It is not substantially removed by dialysis.
Antimicrobial Action: Cefixime is a bactericidal antibiotic and stable to hydrolysis by many beta-lactamases. It has a mode of action and spectrum of activity similar to those of the third-generation cephalosporin cefotaxime, but some Enterobacteriaceae are less susceptible to cefixime. Haemophilus influenzae, Moraxella catarrhalis (Branhamella catarrhalis) and Neisseria gonorrhoea are sensitive, including penicillinase producing strains. Of the Gram-positive bacteria, streptococci are sensitive to cefixime but most strains of staphylococci, enterococci, and Listeria spp. are not.