Monitoring of blood cyclosporine concentration in steroid-resistant nephrotic syndrome.
OBJECTIVE
Cyclosporine has been used for patients with nephrotic syndrome. Because of substantial inter- and intra-patient variability and a narrow therapeutic window, drug monitoring of cyclosporine is mandatory. To confirm the therapeutic effects of a cyclosporine microemulsion (CSAME), the absorption profile of the agent after preprandial administration was determined in steroid-resistant patients with refractory nephrotic syndrome.


METHODS
Fourteen patients were enrolled into the study (mean age, 31.2+/-12; 6 men, 8 women). The patients received 1.5 mg/kg of cyclosporine 30 minutes before breakfast for 6 months. Blood cyclosporine concentration was measured 5 times serially: before administration (C0) and at 1-hour intervals until 4 hours after administration of cyclosporine (C1-C4). In addition, area under the concentration-time curve from 0-4 hours (AUC0-4) was calculated.


RESULTS
After 6 months, CSAME showed marked improvement in proteinuria levels (8.3+/-4.8 g/day vs 0.8+/-0.4 g/day, p<0.001). No changes in serum creatinine and urea nitrogen levels were observed. In 83% of the patients, the CSAME peak concentration appeared within 1 hour after administration (C1). A strong positive correlation was noted between AUC0-4 and C1 (R2=0.90312) and C2 (R2=0.78431). The mean steroid (prednisolone) dose was 40 mg/day when CSAME treatment was started, but a lowering of the dose to 17.5 mg/day (p<0.001) was achieved at 6 months after CSAME therapy.


CONCLUSIONS
Preprandial administration of CSAME is effective in steroid-resistant patients with refractory nephrotic syndrome. C1 or C2, but not C0, was a good clinical marker for CSAME exposure.
Naito
Masayo
M
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo.
Takei
Takashi
T
Eguchi
Aya
A
Uchida
Keiko
K
Tsuchiya
Ken
K
Nitta
Kosaku
K
D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004435:Eating; D004655:Emulsions; D005260:Female; D006801:Humans; D008297:Male; D009404:Nephrotic Syndrome / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D011507:Proteinuria / Q000188:drug therapy / Q000209:etiology
D018501:Antirheumatic Agents; D004655:Emulsions; D016572:Cyclosporine