Pharmacokinetics of omeprazole in patients with liver cirrhosis and extrahepatic portal venous obstruction.
Omeprazole is frequently used in patients with cirrhosis of the liver to treat peptic ulcer disease. It is also used for the healing of mucosal lesions after endoscopic sclerotherapy of esophageal varices in cirrhosis and extraheptic portal vein obstruction (EHPVO). This study was carried out with the aim of determining the pharmacokinetics of omeprazole in different degrees of liver cirrhosis and in patients with EHPVO, compared with healthy volunteers. Ten healthy volunteers, 30 patients with cirrhosis of the liver, divided into 3 groups of 10 depending on severity (according to Child-Pugh classification A, B and C) and ten patients with EHPVO participated in the study. The subjects received an omeprazole 20 mg capsule after an overnight fast. Blood samples were collected at 0, 0.5, 1, 1.5, 2, 2.5, 3, 6, 9 and 24 h after drug administration. Omeprazole level in plasma was estimated by reverse-phase high performance liquid chromatography (HPLC). The elimination half-life was significantly (p < 0.05) increased to 2.38 +/- 0.16, 3.26 +/- 0,12, 3.58 +/- 0.31 and 2.59 +/- 0.22 h in patients with different grades of cirrhosis (A, B and C) and also in patients with EHPVO, respectively, compared with 1.054 + 0.10 h in healthy volunteers. A similar significant increase (p < 0.05) was observed in the AUC(0alpha), while C(max) was significantly increased to 400.40 +/- 27.89 and 602 +/- 55.13 ng/ml in only grade C cirrhosis patients and EHPVO patients, compared with 303.5 +/- 36.42 ng/ml in healthy volunteers. No significant difference was observed in T(max). It was concluded that the metabolism of omeprazole was significantly impaired in both liver cirrhosis and EHPVO in comparison with healthy volunteers.
Kumar
R
R
Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India 160-012. medinst@pgi.chd.nic.in
Chawla
Y K
YK
Garg
S K
SK
Dixit
R K
RK
Satapathy
S K
SK
Dhiman
R K
RK
Bhargava
V K
VK
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D002214:Capsules; D002851:Chromatography, High Pressure Liquid; D006504:Hepatic Veno-Occlusive Disease / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011169:Portal Vein / Q000503:physiopathology; D012189:Retrospective Studies
D002214:Capsules; D009853:Omeprazole