Benefits of cyclosporine absorption profiling in nephrotic syndrome: preprandial once-daily administration of cyclosporine microemulsion improves slow absorption and can standardize the absorption profile.
OBJECTIVE
Cyclosporine is known to improve proteinuria in nephrotic syndrome (NS), but is also associated with drug-related renal impairment. In this case series, therapeutic drug monitoring using the absorption profile was applied to adults with NS to investigate the efficacy and safety of once-daily administration of cyclosporine microemulsion (CSAME).


METHODS
Twenty patients received CSAME starting at 100-175 mg/day (1.4-3.1 mg/kg per day) once daily after breakfast. The area under the concentration-time curve up to 4 h after administration of cyclosporine (AUC(0-4 h)) was determined in each patient within 1 week after the start of CSAME treatment. Thereafter, the dose of CSAME was adjusted according to the absorption profile.


RESULTS
After 6 months, treatment with CSAME improved efficacy test values compared with those prior to treatment, and the severe nephrotic state was eliminated in all patients. No changes in serum creatinine or blood urea nitrogen levels were observed. The dose of CSAME was adjusted so that AUC(0-4 h) and the peak level fell within the range of target values, resulting in a significant decrease in the mean dose of cyclosporine (P = 0.0001). Time of peak level was variable among patients, but when CSAME was administered before breakfast, good absorption was achieved in all patients.


CONCLUSIONS
By monitoring the absorption profile in patients with NS, a once-daily administration of CSAME was used to achieve both efficacy and a reduction in total exposure to the drug. Preprandial administration provided a more stable absorption profile of cyclosporine. The authors hope this method will become standard procedure during cyclosporine treatment in these patients.
Takeda
Asami
A
Nagoya Daini Red Cross Hospital - Kidney Center, Nagoya, Japan. asamit@nagoya2.jrc.or.jp
Horike
Keiji
K
Onoda
Hiroshi
H
Ohtsuka
Yasuhiro
Y
Yoshida
Astuhiro
A
Uchida
Kazuharu
K
Morozumi
Kunio
K
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004339:Drug Compounding; D016903:Drug Monitoring; D004655:Emulsions; D005215:Fasting; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000378:metabolism; D019518:Postprandial Period; D016896:Treatment Outcome
D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine