More Stable and Reliable Pharmacokinetics with Preprandial Administration of Cyclosporine Compared with Postprandial Administration in Patients with Refractory Nephrotic Syndrome

Kusaba, Tetsuro; Konno, Y.; Hatta, Shigeo; Fujino, Tomoya; Yasuda, Takashi; Miura, Hiroki; Sasaki, Hiroyo; Okabayashi, Jun; Murao, Mei; Sakurada, Tsutomu; Imai, Goro; Shirai, Sayuri; Kuboshima, Shingo; Shima, Yoshinori; Ogimoto, Goichi; Sato, Takeo; Masuhara, Keiso; Kimura, Kenjiro

doi:10.1592/phco.25.1.52.55617

Cited by 17 publications

(25 citation statements)

References 17 publications

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“…When CSAME is administered preprandially, the bile acids and the drug would be effectively mixed before food enters the upper gastrointestinal tract, which may result in improved cyclosporine absorption (19). Takeda et al (20) (11,20), we would support their data, suggesting that preprandial administration of CSAME is useful to achieve an absorption profile in steroid-resistant nephrotic syndrome. Second, we measured the absorption profile of CSAME in the same patients several times.…”

Section: Discussionsupporting

confidence: 62%

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Monitoring of Blood Cyclosporine Concentration in Steroid-Resistant Nephrotic Syndrome

et al. 2008

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Objective Cyclosporine has been used for patients with nephrotic syndrome. Because of substantial interand 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 (R 2 =0.90312) and C2 (R 2 =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. Conclusion 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.

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Section: Discussionsupporting

confidence: 62%

“…Preprandial administration of CSAME provided a more stable absorption profile in adult patients with refractory nephrotic syndrome (11). However, the dose adjustment of CSAME and the clinical efficacy of this treatment have not been completely investigated.…”

Section: T a B L E 1 P R E P R A N D I A L Ab S O R P T I O N P R Omentioning

confidence: 99%

Monitoring of Blood Cyclosporine Concentration in Steroid-Resistant Nephrotic Syndrome

et al. 2008

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“…Some recent studies also demonstrated that preprandial administration of CyA provided a more stable absorption profile [9,18,23]. With administration preprandially or just before meal, the drug reaches the digestive tract prior to food, and subsequent entry of food into the digestive tract promotes bile secretion; this may be connected with the good absorption of CyA [14]. In our institution, CyA is administered just before breakfast and dinner because we take into consideration not only improvement of drug absorption but also medication compliance.…”

Section: Discussionmentioning

confidence: 96%

“…However, Nozu et al reported that in an investigation on absorption profiles of 60 nephrotic syndrome patients receiving Neoral® with a mean age of 7.4 years (range 1-20 years), of these patients Cmax was reached after 3 h in 22, who were called late absorbers [20]. The reason why [14]. Some recent studies also demonstrated that preprandial administration of CyA provided a more stable absorption profile [9,18,23].…”

Section: Discussionmentioning

confidence: 99%

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Age effect on whole blood cyclosporine concentrations following oral administration in children with nephrotic syndrome

Ushijima¹,

Uemura²,

Yamada³

2011

Eur J Pediatr

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The aim of this study was to investigate age-related pharmacokinetic differences of cyclosporine (CyA) in children with nephrotic syndrome. Whole blood concentrations of CyA were monitored for a total of 96 times in 36 cases. The 25 male and 11 female patients ranged in age from 1.9 to 19.7 years with a mean age of 9.1 years. Renal biopsy showed minimal change in 33 patients and focal segmental glomerulosclerosis in three patients. CyA was orally administered in two divided doses just before meals. The doses of CyA administered were adjusted such that the target value for blood concentration at 2 h post-dose (C2) was 400-450 ng/ml. The 96 subjects were divided into three groups according to age: group I, 1-5 years (n = 30); group II, 6-10 years (n = 34); and group III, ≥ 11 years (n = 32). In all subjects, peak levels (Cmax) of CyA were reached at C1 or C2. There was no significant difference between the groups for C2, area under the whole blood concentration-time curve up to 4 h post-dose (AUC0-4), and Cmax. The mean CyA doses of groups I, II, and III were 4.8 ± 1.0 mg/kg/day, 3.8 ± 0.9 mg/kg/day, and 3.0 ± 0.6 mg/kg/day, respectively, and there were significant differences between every two groups. In addition, the dose-normalized Cmax (Cmax/dose) and AUC0-4 (AUC0-4/dose) values were significantly lower in the younger group than in the older group. These findings suggested that in children, when the same concentration is targeted, the required CyA dose would vary according to age but would be significantly higher for the younger children.

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Preprandial C2 monitoring of cyclosporine treatment in children with nephrotic syndrome

et al. 2005

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More Stable and Reliable Pharmacokinetics with Preprandial Administration of Cyclosporine Compared with Postprandial Administration in Patients with Refractory Nephrotic Syndrome

Abstract: Preprandial administration provided a more stable absorption profile of cyclosporine compared with postprandial administration. From the correlation with AUC 0-4 , we concluded that C 2 , and not C 0 , is a reliable marker for monitoring cyclosporine exposure.

Cited by 17 publications

References 17 publications

Monitoring of Blood Cyclosporine Concentration in Steroid-Resistant Nephrotic Syndrome

Monitoring of Blood Cyclosporine Concentration in Steroid-Resistant Nephrotic Syndrome

Age effect on whole blood cyclosporine concentrations following oral administration in children with nephrotic syndrome

Preprandial C2 monitoring of cyclosporine treatment in children with nephrotic syndrome

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