Ranitidine disposition and systemic availability in hepatic cirrhosis.

Area of Science:

• Pharmacology
• Hepatology
• Drug Metabolism

Background:

• Cirrhosis can alter drug pharmacokinetics due to impaired liver function.
• Ranitidine is a commonly used medication whose metabolic pathways may be affected by liver disease.

Purpose of the Study:

• To investigate the single-dose pharmacokinetics of ranitidine in patients with stable cirrhosis.
• To determine if cirrhosis significantly impacts ranitidine disposition, including absorption, distribution, metabolism, and excretion.

Main Methods:

• A randomized crossover study design was used in 10 clinically stable patients with biopsy-proven cirrhosis.
• Ranitidine was administered orally (150 mg) and intravenously (50 mg) in single doses after an overnight fast.
• Pharmacokinetic parameters including terminal half-life (t1/2), total plasma clearance, volume of distribution, and systemic availability (AUC) were analyzed.

Main Results:

• The terminal half-life of ranitidine was comparable after oral (2.7 ± 0.4 hr) and intravenous (2.9 ± 0.4 hr) administration.
• Systemic availability was 58% ± 11%, with considerable intersubject variability observed in oral dosing profiles.
• Total plasma clearance was 470 ± 170 ml/min, and steady-state volume of distribution was 1.2 ± 0.2 L/kg.

Conclusions:

• Ranitidine disposition in stable cirrhosis patients was not significantly altered.
• Minor pharmacokinetic variations observed are likely due to physiological changes rather than direct effects of cirrhosis on drug metabolism.