Pharmacokinetics of esomeprazole in Thai patients with liver cirrhosis

Abstract

The present studies aimed to investigate pharmacokinetic properties of esomeprazole, a new proton pump inhibitor which has been registered in Thailand since 2000 in 14 Thai cirrhotic patients compared to 12 Thai healthy volunteers with normal liver function. Each group received 20 mg of esomeprazole orally once a day for 5 consecutive days. It was found that among all pharmacokinetic parameters tested, cirrhotic patients exhibit C[subscript max] and t[subscript max] similar to those observed in normal healthy volunteers whereas significantly higher values of AUC and T[subscript 1/2] were noted in both day 1 and day 5 of the experiments. As expected, clearance of esomeprazole which is extensively metabolized by hepatic cytochrome P450 was markedly reduced in Thai cirrhotic patients and subsequently AUC and T[subscript 1/2] were prolonged. Similar results have previously been reported in Swedish patients, with hepatic impairment, taking 40 mg of esomeprazole. However, t[subscript 1/2] of esomeprazole in both Thai healthy volunteers as well as Thai cirrhotic patients inthe present studies was found to be higher than their corresponding value in Swedish patients. These might be explained by different activity of CYP2C19, a major hepatic metabolizing enzyme of esomeprazole, in which poor metabolizers is more prominent in Asian ethnic group. Additional phenotyping or genotyping study of CYP2c19 in Thai population are needed to clarify this finding. Despite higher values of AUC and t[subscript 1/2] in the study population, the advese effect of esomeprazole observed in both groups was mild and reversible upon cessation of medication. Diarrhea was the most frequently reported side effects. Based on these findings, it can be concluded that esomeprazole 20 mg is well tolerated in the population studied and dose adjustment in cirrhotic patients is not essentially required. However, for the sake of safety, it is suggestive to do the bridging pharmacokinetic studies of drugs that are metabolized mainly by hepatic enzymes that could be different in different ethnic groups, especially those drugs with narrow therapeutic index.