Drug metabolism in liver disease

Oral Disposition Kinetics of Ofloxacin in Patients with Compensated Liver Cirrhosis

“…Although such a change in the volume of distribution of the ter minal phase is theoretically predicted only for drugs highly bound to plasma proteins, it should be noted that an increase in this pa rameter has been observed in cirrhosis also with ampicillin, a drug with a degree of plasma protein binding (20-30%) similar to that of ofloxacin. It is unlikely that a decrease in oral availability may have been responsible for the increase in the distribution volume of ofloxa cin, since the bioavailability is either un changed or increased in liver cirrhosis [14,15]. Although our controls were somewhat youn ger than the cirrhotic patients, the difference in age does not appear to be responsible for the reduction in the renal clearance of ofloxa cin observed in the latter subjects, since both groups had comparable values of either serum creatinine or creatinine clearance, and there was no correlation between renal clearance of ofloxacin and age of the subjects.…”

“…This lengthening of the elimination halflife appears to be the result of either a reduc tion in the renal clearance or an increase in the apparent volume of distribution of the drug. An increased volume of distribution is frequently encountered in cirrhosis and other liver diseases also in the absence of hypoalbuminemia [14,15]. It is thought to be the conse quence of a reduction in plasma protein bind ing caused by accumulation of endogenous competing substances [16,17].…”

Pharmacokinetics of minoxidil in patients with cirrhosis and healthy volunteers

“…Although conjugative pathways are reported to be less affected by hepatic dysfunction than oxidative pathways [4,5], the extensive metabolism that minoxidil undergoes presents a potential for significant changes in its pharmacokinetics in the presence of compromised hepatic function.…”

“…transaminases, alkaline phosphatase) are used as indicators, often in conjunction with measurement of bilirubin and blood clotting times, although transaminase concentrations can be misleading [5,6]. Biopsy of the liver is considered the 'gold standard' for diagnosing liver disease, but its accuracy is limited to the section of liver sampled [5]. Usually performed percutaneously with a needle, hepatic biopsy may identify the only damaged tissue in the entire organ, or may capture the only healthy tissue from a patient with substantial hepatic damage.…”

“…In clinical medicine, serum concentrations of albumin and hepatic enzymes (e.g. transaminases, alkaline phosphatase) are used as indicators, often in conjunction with measurement of bilirubin and blood clotting times, although transaminase concentrations can be misleading [5,6]. Biopsy of the liver is considered the 'gold standard' for diagnosing liver disease, but its accuracy is limited to the section of liver sampled [5].…”