Oral pharmacokinetics of cyclosporin in patients with primary biliary cirrhosis and patients with skin diseases.
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 non-specific (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.
Beukers
R
R
Department of Internal Medicine II, University Hospital Dijkzigt, Rotterdam, The Netherlands.
de Rave
S
S
van den Berg
J W
JW
Schalm
S W
SW
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007408:Intestinal Absorption; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D012871:Skin Diseases / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D016572:Cyclosporine