Single-dose pharmacokinetics of fluconazole in patients with liver cirrhosis

The pharmacokinetics of a single 100 mg i.v. dose of fluconazole were studied in parallel groups of ten normal subjects and nine patients with liver cirrhosis, a condition with a high risk of life-threatening fungal infection. The following mean pharmacokinetic parameters were found for the patient group: terminal elimination constant 0.0101/h (normal 0.0214/h); mean residence time 134 h (normal 46.7h); area under the curve 200 h.mg/L(normal 69.4 h.mg/L); plasma clearance 0.96 L/h.kg(normal 2.16 L/h.kg). All these differences were statistically significant (P < 0.05). The majority of the patients were being concomitantly treated with duretics (frusemide and spironolactone). It is suggested that the known slight interaction between such drugs and fluconazole was intensified by the disease state. These results emphasize the need for caution in the treatment with fluconazole of patients with severe liver disease. Nevertheless, in view of the wide range of values found in the patients, and low toxicity of fluconazole, a dosage reduction in cirrhosis does not seem to be justified in the present state of knowledge.