Cefpiramide kinetics and plasma protein binding in cholestasis

Area of Science:

• Pharmacology
• Hepatology
• Clinical Pharmacy

Background:

• Cefpiramide is a novel parenteral cephalosporin primarily eliminated via bile.
• Cholestasis significantly impacts drug metabolism and excretion pathways.
• Understanding cefpiramide's pharmacokinetics in cholestasis is crucial for safe and effective therapeutic use.

Purpose of the Study:

• To investigate the pharmacokinetic profile of cefpiramide in patients with cholestasis compared to healthy subjects.
• To evaluate the impact of cholestasis on cefpiramide's clearance, elimination half-life, and excretion routes.
• To determine the necessity of modifying cefpiramide dosage regimens in cholestatic individuals.

Main Methods:

• Single 1 g intravenous dose of cefpiramide administered to 8 cholestatic patients and 11 healthy controls.
• Cefpiramide plasma and urine concentrations quantified using high-performance liquid chromatography (HPLC).
• Plasma protein binding assessed via ultrafiltration.

Main Results:

• Total clearance of cefpiramide was significantly lower in cholestatic patients (15.5 mL/min) versus healthy subjects (25.6 mL/min).
• The terminal elimination half-life of cefpiramide was prolonged in patients with cholestasis (12.0 h) compared to healthy individuals (5.3 h).
• Urinary recovery of unchanged cefpiramide was substantially higher in cholestatic patients (85.1%) due to impaired biliary excretion, and plasma protein binding was reduced (fu = 0.23).

Conclusions:

• Cholestasis significantly alters cefpiramide pharmacokinetics, leading to reduced clearance and extended half-life.
• Impaired biliary elimination in cholestasis results in increased urinary excretion of cefpiramide.
• Dosage regimen adjustments for cefpiramide are recommended in patients with cholestasis to ensure optimal therapeutic outcomes.