Mode of Excretion of Zifi (Cefixime)
Cefixime is primarily excreted unchanged in the urine (approximately 50% of the absorbed dose within 24 hours) and significantly through biliary excretion into the bile (approximately 5-10% of the administered dose), with no evidence of metabolic transformation in vivo. 1
Renal Excretion
Approximately 50% of the absorbed dose of cefixime is excreted unchanged in the urine within 24 hours, representing the primary route of elimination. 1
Urinary excretion studies show that 11.9-14.5% of the administered dose appears in urine as unchanged drug, with renal clearance averaging 39.1 mL/min in patients with normal renal function. 2, 3
The drug is not significantly cleared by hemodialysis or peritoneal dialysis, which is an important consideration for patients with end-stage renal disease. 1
Biliary Excretion
Cefixime demonstrates significant biliary excretion, with levels in bile being 20-25 fold higher than concurrent serum levels. 4
In patients with external biliary drainage, approximately 5% of the oral dose is recovered in bile over 24 hours, with peak bile concentrations reaching 56.9 mg/L compared to serum peak of 2.3 mg/L. 4
Bile levels remain therapeutically relevant even 20 hours after dosing (mean 4.3 mg/L), suggesting sustained biliary excretion. 4
Animal studies confirm that cefixime is excreted in bile in excess of 10% of the administered dose. 1
Absence of Metabolism
There is no evidence of metabolism of cefixime in vivo, distinguishing it from many other antibiotics that require hepatic biotransformation. 1
The lack of metabolic transformation means that both renal and biliary routes excrete the parent compound unchanged, which is clinically significant for maintaining antibacterial activity. 1
Clinical Implications for Renal Impairment
In moderate renal impairment (creatinine clearance 20-40 mL/min), the serum half-life of cefixime is prolonged to 6.4 hours (compared to 3-4 hours in normal subjects). 1
In severe renal impairment (creatinine clearance 5-20 mL/min), the half-life increases to 11.5 hours, necessitating dose adjustment. 1
Dose reduction is only necessary in patients with severe renal failure (creatinine clearance below 20 mL/min), as biliary excretion can partially compensate for reduced renal clearance. 2
Pharmacokinetic Summary
The serum half-life averages 3-4 hours in healthy subjects but may range up to 9 hours in some individuals, independent of dosage form. 1
Approximately 40-50% of cefixime is absorbed orally, with the remaining unabsorbed drug likely excreted in feces. 1
The dual excretory pathway (renal + biliary) accounts for the fact that only 50-60% of the absorbed dose is recovered in urine and bile combined, with the remainder potentially undergoing fecal excretion of unabsorbed drug. 1, 4