Liver Cirrhosis Research Today is a free monthly online journal that collates and summarizes the latest research about Liver Cirrhosis, including details on alcohol, treatment, drugs, effects, causes. | ||||||||
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Pharmacokinetics of pitavastatin in subjects with Child-Pugh A and B cirrhosis.Hui CK, Cheung BM, Lau GK Department of Medicine, University of Hong Kong, Hong Kong. AIM: Lipid lowering therapy with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors is increasingly used for the prevention of cardiovascular events, but they should be used with caution in patients with impaired liver function. We therefore studied the pharmacokinetics of pitavastatin in patients with liver cirrhosis. METHODS: Plasma concentrations of pitavastatin were determined after administration of 2 mg single-dose pitavastatin to 12 male patients with liver cirrhosis (six Child-Pugh grade A and six grade B). These results were compared with the single-dose pharmacokinetic results obtained from six male volunteers without liver disease. RESULTS: Administration of 2 mg single-dose pitavastatin to patients with Child-Pugh grade A and grade B cirrhosis resulted in a 1.19- and 2.47-fold increase in Cmax and 1.27- and 3.64-fold increase in AUCt, respectively, when compared with normal subjects. The geomean Cmax of pitavastatin was 59.5 ng ml(-1), 70.7 ng ml(-1) and 147.1 ng ml(-1) in the control, Child-Pugh grade A and Child-Pugh grade B groups, respectively. The geomean AUCt of pitavastatin in the three groups was 121.2 ng h(-1) ml(-1), 154.2 ng h(-1) ml(-1) and 441.7 ng h(-1) ml(-1), respectively. The geomean Cmax of pitavastatin lactone was 20.3 ng ml(-1), 19.1 ng ml(-1) and 9.9 ng ml(-1) in the control, Child-Pugh grade A and grade B groups, respectively. The AUCt of pitavastatin lactone was 120.2 h(-1) ml(-1), 108.8 h(-1) ml(-1) and 87.5 h(-1) ml(-1), respectively. CONCLUSION: The plasma concentration of pitavastatin is increased in patients with liver cirrhosis. In such patients, caution is required, although dose reduction may not be necessary in Child-Pugh A cirrhosis. Published 8 March 2005 in Br J Clin Pharmacol, 59(3): 291-7.
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