Oral pharmacokinetics of cyclosporin in patients with primary biliary Cirrhosis and patients with skin diseases

SUMMARY The pharmacokinetics of cyclosporin after oral administration were studied in seven patients with non‐end stage primary biliary cirrhosis (PBC) without previous cyclosporin treatment (Group I), a control group of nine patients with skin diseases (mainly psoriasis; Group II) and six patients with PBC after prolonged cyclosporin treatment (Group III). Whole blood concentrations of cyclosporin were measured using a nonspecific (N) radioimmunoassay (RIA) and — in a majority of the cases—also by a RIA specific (S) for the parent drug. No difference in cyclosporin absorption was observed between patients with PBC and those with a skin disease. The mean values for the area under the blood concentration‐time curve for the first 6 h after the test dose (AUC0‐6) and the maximal blood concentrations (Cmax) were significantly higher for Group I compared with Group II patients (P= 0.007 and 0.03, respectively), but the time to maximal blood concentrations (tc, max) did not differ. There was a trend toward higher mean AUC0‐6 (P= 0.08) and Cmax (P= 0.08) values for Group III compared with Group I patients. Tc, max values were not influenced by prolonged cyclosporin treatment. The ratio of cyclosporin whole blood concentrations measured by the non‐specific and specific RIA'S (N/S ratio) increased with time without obvious differences between the three groups. These data suggest that cyclosporin absorption and its biotransformation in the liver are not impaired in patients with non‐end stage PBC and that neither is affected by prolonged treatment.