Pharmacokinetics of ampicillin in cirrhosis

Ampicillin pharmacokinetics was studied in 9 cirrhotic patients and in 8 healthy subjects to assess liver disease-related differences in distribution, elimination, and bioavailability of ampicillin. Plasma, urine, and ascites fluid samples were analyzed microbiologically. After intravenous doses, the cirrhotic patients have lower initial plasma concentrations of ampicillin because of the larger volume of distribution. Such patients usually have diminished renal function, which, because renal tubular secretion is the main route of excretion of ampicillin, causes prolonged retention of ampicillin. Metabolic-biliary clearance of ampicillin, normally accounting for removal of only 10% of the dose in normal subjects, is three times as great in cirrhotic patients. Peak ascites fluid concentrations of ampicillin ranged from 2 to 7 mcg/ml after 600 mg iv doses, and very slow clearance of ampicillin from the peritoneal cavity results in persistence in this compartment. Though absorption of ampicillin from capsules was often erratic, its bioavailability was similar in normal and cirrhotic subjects. These findings suggest that the usual course of ampicillin therapy of infections should not be altered in cirrhotic patients. On the other hand, reduction in dosage may be called for when there is renal impairment.