Evaluation of the therapeutic range of whole blood cyclosporin concentration in the treatment of psoriasis.
Cyclosporin (CyA) trough levels in whole blood in 17 patients receiving CyA for the treatment of severe psoriasis were measured by fluorescence polarization immunoassay (FPIA) employing a specific monoclonal antibody. Clinical success was defined as a PASI score reduction greater than or equal to 75% (group A), partial success by a PASI score reduction of 60%-74% (group B), and insufficient efficacy by a PASI score reduction of less than 60% (group C). Nine of the 17 patients given CyA (53%) exhibited an improvement rate of > or = 75% in the PASI score within 8 weeks of the initiation of treatment. At 8 weeks of treatment the values for the daily dose and whole blood trough CyA concentration were both significantly higher in group A than in group C, daily dose (3.6 +/- 1.0 vs. 2.3 +/- 0.4 mg/kg/day, respectively) and whole blood concentration (141.3 +/- 46.0 vs. 79.7 +/- 19.0 ng/ml). Throughout the study period, during an average observation period of 30 weeks, 13 of the 17 patients (76%) achieved a reduction rate of > or = 75% in the PASI score. In these 13 patients in whom psoriasis lesions cleared satisfactorily the values for the mean daily CyA dose, and whole blood trough levels were 2.4 mg/kg/day and 94.8 ng/ml, respectively. The improvement rate was significantly higher when the CyA trough level was above, rather than below, 100-140 ng/ml within the first 8 weeks, although a lower CyA dose and/or whole blood level was effective in maintaining the reduced PASI score in the subsequent phase. The most important side-effect was mild hypertension in 7 of the 17 patients (41%), however, the onset of hypertension in these patients varied from 30-100 days after the initiation of treatment. Antihypertensive drug therapy and/or dose reduction resulted in a significant decrease, from 166 +/- 17/100 +/- 7-140 +/- 6/84 +/- 10 mmHg, of the CyA-induced hypertension. The relationship between the time course of the duration of improved PASI score and the whole blood concentration of CyA was observed, which suggests that the changes in drug effects were correlated with changes in whole blood levels. During the study period we experienced recurrences in 2 patients after the tapering or withdrawal of CyA treatment. In these 2 patients the relapse may have been due, in part, to the sharp decrease in whole blood concentration secondary to partial noncompliance. Measurement of whole blood CyA trough level is the only method for assessing the patient's noncompliance. Contrary to previous reports we confirmed that the measurement of CyA concentration in whole blood was useful for monitoring the effects in patients with psoriasis.
Ieiri
I
I
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Nakayama
J
J
Murakami
H
H
Hori
Y
Y
Higuchi
S
S
D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016231:Fluorescence Polarization Immunoassay; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*
D007166:Immunosuppressive Agents; D016572:Cyclosporine