Pharmacokinetics of roxatidine acetate in patients with chronic liver disease.
OBJECTIVE
Patients with liver disease are prone to develop peptic ulceration and often receive H(2)-receptor antagonists. Therefore, it is important to clarify whether the pharmacokinetics of H(2)-receptor antagonists is affected by hepatic function. However, pharmacokinetics of a new H(2)-receptor antagonist, roxatidine acetate, in chronic liver disease has not been well known. In this study, we analyzed the pharmacokinetics of roxatidine in patients with liver disease.


METHODS
Blood samples were obtained from 11 patients with chronic hepatitis, 11 patients with cirrhosis and six healthy subjects. Under fasting conditions, 75 mg of roxatidine acetate was administered orally, and plasma roxatidine levels were determined sequentially from 3 to 12 h. Relationships between pharmacokinetic variables and each parameter related to hepatic functions were also investigated.


RESULTS
There was no difference in the pharmacokinetic variables and serum levels of roxatidine between chronic hepatitis and healthy controls. In contrast, in cirrhosis, serum roxatidine levels were significantly higher than those in chronic hepatitis and normal control. Half-life, the area under the plasma concentration-time curve and clearance in cirrhosis were also significantly longer, bigger and smaller than those in chronic hepatitis and healthy controls, respectively. The half-life became longer and the clearance became smaller in parallel with the progression of liver disease. Serum levels of hyaluronate and gamma-glutamyl transpeptidase showed a good correlation with half-life, clearance and elimination rate. A good correlation between creatinine clearance and elimination rate was found.


CONCLUSIONS
Pharmacokinetics of roxatidine acetate is affected by hepatic function, and the dosage of roxatidine acetate for patients with liver disease, especially cirrhosis, should be modified.
Tsutsumi
M
M
Division of Gastroenterology, Department of Internal Medicine, Kanazawa Medical University, Uchinada, Ishikawa, Japan. tsutsumi@kanazawa-med.ac.jp
Ueshima
Y
Y
Takase
S
S
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D002908:Chronic Disease; D003404:Creatinine / Q000378:metabolism; D006207:Half-Life; D019698:Hepatitis C, Chronic / Q000150:complications / Q000378:metabolism*; D006635:Histamine H2 Antagonists / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000378:metabolism*; D008111:Liver Function Tests; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010437:Peptic Ulcer / Q000188:drug therapy / Q000209:etiology; D010880:Piperidines / Q000493:pharmacokinetics* / Q000627:therapeutic use
D006635:Histamine H2 Antagonists; D010880:Piperidines; D003404:Creatinine; C053742:roxatidine acetate