Single-dose ceftriaxone kinetics in liver insufficiency.

Area of Science:

• Pharmacology
• Hepatology
• Nephrology

Background:

• Ceftriaxone is a widely used antibiotic.
• Chronic liver disease can alter drug disposition.
• The impact of liver disease on ceftriaxone pharmacokinetics requires clarification.

Purpose of the Study:

• To investigate the disposition of ceftriaxone in patients with chronic liver disease.
• To assess the influence of liver damage severity and renal impairment on ceftriaxone pharmacokinetics.

Main Methods:

• Administered 1 gm intravenous bolus ceftriaxone to healthy subjects and patients with fatty liver or cirrhosis.
• Measured plasma protein binding, free fraction, and renal/nonrenal clearance.
• Analyzed pharmacokinetic parameters, including elimination half-life.

Main Results:

• Plasma protein binding of ceftriaxone decreased significantly in subjects with liver disease, increasing the free fraction.
• Nonrenal clearance of unbound ceftriaxone decreased with increasing liver damage severity.
• Renal clearance of unbound ceftriaxone remained similar to healthy adults, except in cases of combined liver and renal impairment.

Conclusions:

• Despite increased free ceftriaxone concentrations in liver disease, dose adjustments are generally not needed due to its wide therapeutic range.
• Dose reduction may be considered for patients with cirrhosis and ascites, particularly if renal function is also impaired, due to higher unbound drug levels.