Triolev-200/Triolev Mechanism of Action

Triolev-200: Pharmacotherapeutic group: Third generation cephalosporin.
Pharmacology: Pharmacodynamics: Cefixime is an oral third generation cephalosporin which has marked in vitro bactericidal activity against a wide variety of Gram-positive and Gram-negative organisms. Clinical efficacy has been demonstrated in infections caused by commonly occurring pathogens including Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli, Proteus mirabilis, Klebsiella species, Haemophilus influenzae (beta-lactamase positive and negative strains), Branhamella catarrhalis (beta-lactamase positive and negative) and Enterobacter species. It is highly stable in the presence of beta-lactamase enzymes. Most strains of Enterococci (Streptococcus faecalis, group D Streptococci) and Staphylococci (including coagulase positive and negative strains and methicillin-resistant strains) are resistant to Cefixime. In addition, most strains of Pseudomonas, Bacteroides fragilis, Listeria monocytogenes and Clostridia are resistant to Cefixime.
Pharmacokinetics: The absolute oral bioavailability of Cefixime is in the range of 22-54%. Absorption is not significantly modified by the presence of food. Cefixime may therefore be given without regard to meals. From in vitro studies, serum or urine concentrations of 1 mcg/mL or greater were considered to be adequate for most common pathogens against which Cefixime is active. Typically, the peak serum levels following the recommended adult or pediatric doses are between 1.5 and 3 mcg/mL. Little or no accumulation of Cefixime occurs following multiple dosing.
The pharmacokinetics of Cefixime in healthy elderly (age >64 years) and young volunteers (11-35). Compared the administration of 400 mg doses once daily for 5 days. Mean Cmax and AUC values were slightly greater in the elderly. Elderly patients may be given the same dose as the general population. Cefixime is predominantly eliminated as unchanged drug in the urine. Glomerular filtration is considered the predominant mechanism. Metabolites of Cefixime have not been isolated from human serum or urine. Serum protein binding is well characterised for human and animal sera; Cefixime is almost exclusively bound to the albumin fraction, the mean free fraction being approximately 30%. Protein binding of Cefixime is only concentration dependent in human serum at very high concentrations which are not seen following clinical dosing.
Transfer of 14C-labelled Cefixime from lactating rats to their nursing offspring through breast milk was quantitatively small (approximately 1.5% of the mothers' body content of Cefixime in the pup). No data are available on secretion of Cefixime in human breast milk. Placental transfer of Cefixime was small in pregnant rats dosed with labelled Cefixime.
Triolev: Pharmacotherapeutic group: Antibacterial for systemic use, belonging to the class of cephalosporins.
Pharmacology: Pharmacodynamics: Mode of action: Cefixime is an antibiotic belonging to the third generation cephalosporin group. Like other cephalosporins, cefixime exerts antibacterial activity by binding to and inhibiting the action of penicillin-binding proteins involved in the synthesis of bacterial cell walls. This leads to bacterial cell lysis and cell death.
Mechanism of resistance: Bacterial resistance to cefixime may be due to one or more of the following mechanisms: Hydrolysis by extended-spectrum beta-lactamases and/or by chromosomally-encoded (AmpC) enzymes that may be induced or de-repressed in certain aerobic gram negative bacterial species; Reduced affinity of penicillin-binding proteins; Reduced permeability of the outer membrane of certain gram-negative organisms restricting access to penicillin-binding proteins; Drug efflux pumps.
More than one of these mechanism of resistance may co-exist in a single bacterial cell. Depending on the mechanism(s) present, bacteria may express cross-resistance to several or all beta-lactams and/or antibacterial drugs of other classes.
Pharmacokinetics: Cefixime, given orally is about 40% to 50% absorbed whether administered with or without food; however, time for maximal absorption is increased approximately 0.8 hours when administered with food without alteration in other pharmacokinetic parameters. A single 200 mg tablet of Cefixime produces an average peak serum concentration of approximately 2.7 mcg/mL. No biologically active metabolites of Cefixime have been discovered. It is approximately 70% protein bound. Very high concentration is found in bile and hence used in biliary tract infections. The mean elimination half life is 3 hours. Urinary excretion accounts for between 12% to 34% of orally administered dose. The biliary recovery of Cefixime in 24 hours is 5% of orally administered dose.
The t_1/2 is prolonged in patients with severely impaired renal function. Hence dosage adjustment is necessary in severe renal impairment i.e. Creatinine clearance <20 mL/min. Peak serum concentration following oral administration of the absorbed dose is excreted unchanged in the urine in 24 hours.