Disposition of quinine and its major metabolite, 3- hydroxyquinine in patients with liver diseases
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Chinedum P. Babalola1*, Olayinka A. Kotila1, Patrick A. F. Dixon2 and Adefemi E. Oyewo3
- چاپ و سال / کشور: 2011
Description
Quinine, extensively metabolized by CYP 3A4, has 3-hydroxyquinine as the major metabolite which also contributes to its antimalarial activity. This study assessed the impact of various liver diseases on the disposition of quinine and 3-hydroxyquinine. Ten adult patients with liver diseases ranging from cirrhosis, primary liver carcinoma, hepatitis, ascites, and amoebic liver disease as well as six healthy subjects received single oral dose of 600 mg quinine sulphate tablets. Venous blood and urine were collected over 48 h. Quinine and 3-hydroxyquinine were determined from the matrices by a validated high performance liquid chromatography (HPLC) method. Wide inter-individual variations were observed in the subjects especially those with liver diseases. Cmax (4.47 vs 2.41mcg/ml) and AUC (73 vs 51mcg.h/ml) values were significantly increased in liver disease patients. Clearance was reduced by 30% from 3.27 to 2.31 (p = 0.009). Metabolic ratio of quinine/3-hydroxyquinine in plasma decreased from 5.5 to 1.42 over 4 to 48 h. Cumulative amount of quinine and 3-hydroxyquinine produced in urine were 38 mg (8%) and 32 mg (7%) respectively. Compromised metabolism of quinine in liver disease patients suggests the necessity of reviewing the dosage of quinine in liver disease patients who come up with malaria, a situation that further reduces liver function.
Research In Pharmaceutical Biotechnology Vol. 3(3), pp. 25-29, March 2011 Available online at http://www.academicjournals.org/rpb ISSN 2141-2324 ©2011 Academic Journals
