Abstract :
Objectives: To determine the pharmacokinetic properties of esomeprazole,a new proton pump inhibi-
tor, which is mainly metabolized by the liver, in Thai cirrhotic patients of various etiologies and healthy controls.
Patients and Methods: The study population included two groups, including 12 cirrhotic patients
with different Child Pugh’s classification (Child A = 4, Child B = 4, Child C = 4) and 12 healthy controls. Each
group received 20 mg. of esomeprazole OD. for 5 consecutive days. Serial blood samples were collected over 10
hours period on the first day (D1) after single dose and the fifth day (D5) of the study after multiple doses for
measurement of plasma esomeprazole levels.
Results: All pharmacokinetic properties of esomeprazole, except T max, were higher in D5 than in the
D1 in both groups. However, when compared between both groups, AUC and half-life in the cirrhotic patients were
higher than those in the healthy group on both D1 and D5. AUC. on D1 of the cirrhotic patients and healthy controls
were 4.7 and 3.2 micromol.hr/l while AUC. on D5 of both groups were 5.9 and 4.2 micromol.hr/l, respectively.
Cirrhotic patients had longer half-life of esomeprazole than healthy controls on both D1 (4.1 and 2.1 hr.) and D5
(4.1 and 2.4 hr.). Although, plasma levels of esomeprazole were elevated in cirrhotic patients when compared with
control group, these findings usually confined to the patients with severely impaired liver function.
Conclusions: Esomeprazole given 20 mg.OD by oral administration for 5 consecutive days resulted in
comparable pharmacokinetic parameters including AUC, half-life in cirrhotic patients and healthy controls. Plasma
levels of esomeprazole were elevated in cirrhotic patients especially in Child C when compared with the control
group. Dose adjustment should not be required except those with Child C cirrhosis and further study need to be
done .
[Thai J Gastroenterol 2005; 6(1): 21-27] |
file/Thai-Journal-of-gastroenterology-vol-6-no-1-2238243.pdf