Grepafloxacin pharmacokinetics in individuals with hepatic dysfunction

Area of Science:

• Pharmacology
• Hepatology
• Infectious Diseases

Background:

• Grepafloxacin is a novel broad-spectrum fluoroquinolone antibiotic.
• Hepatic impairment can significantly alter drug pharmacokinetics.
• Understanding grepafloxacin's behavior in liver disease is crucial for safe dosing.

Purpose of the Study:

• To investigate the pharmacokinetics of oral grepafloxacin in healthy volunteers and patients with varying degrees of hepatic impairment.
• To determine appropriate dosing recommendations for grepafloxacin in patients with liver dysfunction.

Main Methods:

• Two trials were conducted involving healthy volunteers and patients with mild (Child-Pugh Class A) and moderate (Child-Pugh Class B or C) hepatic impairment.
• Participants received a 400 mg oral dose of grepafloxacin daily for 7 days.
• Plasma and urine concentrations of grepafloxacin were measured over 7 days to assess pharmacokinetic parameters.

Main Results:

• Compared to healthy individuals, patients with liver impairment exhibited increased peak plasma concentrations and area under the curve.
• Apparent total clearance of grepafloxacin was reduced in hepatic dysfunction, with greater reductions in more severe impairment.
• Mild hepatic impairment (Class A) showed a 36% increase in peak concentrations and a 33% reduction in clearance.

Conclusions:

• A daily dose of 400 mg grepafloxacin is recommended for patients with mild hepatic impairment.
• Grepafloxacin should be avoided in patients with moderate to severe liver disease due to altered pharmacokinetics and reduced clearance.
• Child-Pugh scores did not correlate with specific pharmacokinetic variables, suggesting a need for cautious dosing based on impairment severity.