Pharmacokinetic and clinical studies with carfecillin

Area of Science:

• Pharmacology
• Clinical Pharmacy
• Drug Metabolism

Background:

• Carbenicillin-phenyl-ester (carfecillin) is an antibiotic.
• Understanding its pharmacokinetic profile is crucial for effective therapeutic use.
• Hepatic and renal functions can significantly impact drug metabolism and excretion.

Purpose of the Study:

• To investigate the pharmacokinetics of carfecillin in healthy subjects, patients with hepatic cirrhosis, and patients with renal insufficiency.
• To assess the impact of hepatic and renal impairment on carfecillin serum levels, metabolism, and excretion.
• To evaluate the clinical efficacy of carfecillin in treating urinary tract infections (UTIs).

Main Methods:

• Pharmacokinetic study involving 10 healthy subjects, 5 patients with hepatic cirrhosis, and 5 patients with renal insufficiency.
• Measurement of serum and urine concentrations of carfecillin and its phenol moiety (free and conjugated).
• Clinical assessment of treatment success in 30 patients with UTIs.

Main Results:

• In healthy subjects, peak serum levels were ~20 microgram/ml and urine concentrations >1000 mu/ml.
• The phenol moiety was mainly excreted as glucuronide and sulfate conjugates.
• Hepatic lesion did not significantly alter pharmacokinetics; renal insufficiency led to higher serum levels and lower urine concentrations of carfecillin and conjugated phenol.

Conclusions:

• Carfecillin pharmacokinetics are significantly affected by renal insufficiency but not by hepatic cirrhosis.
• Carfecillin demonstrated a high success rate (20/30 patients) in treating UTIs.
• The findings support the use of carfecillin, with potential dose adjustments needed in renal impairment.