Prediction of systemic exposure to cyclosporine in Japanese pediatric patients.
The monitoring of the blood concentration at 2 h (C(2)) after the oral administration of a cyclosporine (CsA) microemulsion was reconfirmed to be useful for the prediction of systemic exposure, the area under the blood concentration-time curve from 0 to 4 h (AUC(0-4)), in a group of Japanese patients, consisting of 33 children aged 5-15 years and 19 young adults aged 16-27 years, with a greater correlation for C(2) (r = 0.927) than the trough concentration (r = 0.488). The dose-normalized AUC(0-4) was independent of gender or indications for CsA, while it depended on body size, i.e., the age (P = 0.065) and total body weight (P = 0.026). MDR1 C3435T had a weak, but insignificant effect (P = 0.072); it was about 22-31% lower in the patients with TT(3435). Co-administration of a steroid and further treatment with nifedipine had a more intensive effect (P = 0.018); co-administration resulted in a 51% increase in the dose-normalized AUC(0-4). A strong effect was also observed for the serum total cholesterol level (P = 0.001). Collectively, the discrepancies in the results on MDR1 C3435T among investigators might be due to variability in the age/total body weight, co-administration drugs or serum lipid level.
Sakaeda
Toshiyuki
T
Department of Hospital Pharmacy, School of Medicine, Kobe University, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. sakaedat@med.kobe-u.ac.jp.
Iijima
Kazumoto
K
Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Nozu
Kandai
K
Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Nakamura
Tsutomu
T
Department of Hospital Pharmacy, School of Medicine, Kobe University, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Moriya
Yuka
Y
Department of Hospital Pharmacy, School of Medicine, Kobe University, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Nishikawa
Mika
M
Department of Hospital Pharmacy, School of Medicine, Kobe University, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Wada
Atsushi
A
Department of Hospital Pharmacy, School of Medicine, Kobe University, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Okamura
Noboru
N
Department of Clinical Evaluation of Pharmacotherapy, Kobe University Graduate School of Medicine, 1-5-6, Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
Matsuo
Masafumi
M
Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Okumura
Katsuhiko
K
Department of Hospital Pharmacy, School of Medicine, Kobe University, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.|Department of Clinical Evaluation of Pharmacotherapy, Kobe University Graduate School of Medicine, 1-5-6, Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000493:pharmacokinetics*; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D007564:Japan; D008297:Male; D013997:Time Factors
D007166:Immunosuppressive Agents; D016572:Cyclosporine