Pharmacokinetics of mycophenolic acid in children with clinically stable idiopathic nephrotic syndrome receiving cyclosporine.
BACKGROUND
The suitable dosage regime of mycophenolate mofetil (MMF) based on the pharmacokinetics of mycophenoric acid (MPA) for pediatric patients with idiopathic nephrotic syndrome (INS) is controversial. The pharmacokinetics of MPA is influenced by renal function, serum albumin concentration, and concomitant medications, especially calcineurin inhibitors. This study analyzed the pharmacokinetics of MPA in clinically stable children with INS receiving cyclosporine (CyA).


METHODS
This retrospective study enrolled children with INS receiving MMF (Cellcept®) (30-40 mg/kg/day in two divided doses) combined with CyA (Neoral®) without relapse and renal dysfunction. Pharmacokinetic parameters, including the area under the concentration-time curve (AUC) calculated by the trapezoid method, were calculated from seven serial blood samples.


RESULTS
Thirty-two patients (22 males) of median age 11.0 years were included; 32 pharmacokinetic studies were performed. The median MMF dose was 16.2 mg/kg/time or 470.4 mg/m2/time. The median AUC0-12 was 44.3 ng h/mL. AUC0-12 of all patients showed excellent correlations with C2 (r2= 0.6405, P < 0.0001), resulting in a regression formula of AUC0-12 = 21.971 + 2.6059 C2. Comparisons of dose/body weight-normalized AUC0-12 values among age groups showed a lower value in the youngest group (≤5 years).


CONCLUSIONS
In children with clinically stable INS receiving CyA, C2 monitoring was the most useful single parameter for estimating MPA pharmacokinetics. Younger children required higher MMF doses.
Pediatric Nephrology, Aichi Children's Health and Medical Center, Aichi, Japan. satohibino@yahoo.co.jp.|Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan. satohibino@yahoo.co.jp.
Satoshi
S
Hibino
Pediatric Nephrology, Aichi Children's Health and Medical Center, Aichi, Japan.
Takuhito
T
Nagai
Pediatric Nephrology, Aichi Children's Health and Medical Center, Aichi, Japan.
Satoshi
S
Yamakawa
Pediatric Nephrology, Aichi Children's Health and Medical Center, Aichi, Japan.
Hidekazu
H
Ito
Pediatric Nephrology, Aichi Children's Health and Medical Center, Aichi, Japan.
Kazuki
K
Tanaka
Pediatric Nephrology, Aichi Children's Health and Medical Center, Aichi, Japan.
Osamu
O
Uemura
D000293:Adolescent; D000367:Age Factors; D019540:Area Under Curve; D065095:Calcineurin Inhibitors / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage*; D054796:Drug Dosage Calculations; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D009404:Nephrotic Syndrome / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D012189:Retrospective Studies; D016896:Treatment Outcome
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid
Children; Cyclosporine; Mycophenolate mofetil; Mycophenolic acid; Nephrotic syndrome; Pharmacokinetics