Population pharmacokinetics of mizoribine in pediatric patients with kidney disease

Hisashi Kaneda; Masaki Shimizu; Kazuhide Ohta; Katsumi Ushijima; Yoshimitsu Gotoh; Kenichi Satomura; Takuhito Nagai; Mikiya Fujieda; Masashi Morooka; Takuji Yamada; Masayoshi Yamada; Naohiro Wada; Mari Takaai; Yukiya Hashimoto; Osamu Uemura

doi:10.1007/s10157-015-1209-9

Population pharmacokinetics of mizoribine in pediatric patients with kidney disease

Hisashi Kaneda, Masaki Shimizu^*, Kazuhide Ohta, Katsumi Ushijima, Yoshimitsu Gotoh, Kenichi Satomura, Takuhito Nagai, Mikiya Fujieda, Masashi Morooka, Takuji Yamada, Masayoshi Yamada, Naohiro Wada, Mari Takaai, Yukiya Hashimoto, Osamu Uemura

^*Corresponding author for this work

Clinical Pharmacokinetics

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Background: The present study aimed to obtain information enabling optimisation of the clinical effect of mizoribine (MZR) in pediatric patients with kidney disease. Methods: A total of 105 pediatric patients with kidney disease treated at our institutions were enrolled. Kidney transplant patients were excluded. Population pharmacokinetic analysis of MZR was performed based on serum concentration data. Area under the curve from time zero to infinity (AUC_∞) and maximal concentration (C_max) were calculated by Bayesian analysis. Results: In children, the appearance of MZR in the blood tended to be slower and the subsequent rise in blood concentration tended to be more sluggish, compared to healthy adults. Apparent volume of distribution and oral clearance were also higher in children compared to adults. A significant positive correlation was observed between patient age and AUC_∞. There were significant differences of AUC_∞ and C_max by age group. No relationship was observed between the administration method of MZR and serum concentration. Conclusion: The pharmacokinetics of MZR was different in children compared to adults. To obtain the expected clinical efficacy, the regular MZR dosage schedule (2–3 mg/kg/day) might be insufficient for pediatric patients. In particular, younger patients might require a higher dosage of MZR per unit body weight.

Original language	English
Pages (from-to)	757-763
Number of pages	7
Journal	Clinical and Experimental Nephrology
Volume	20
Issue number	5
DOIs	https://doi.org/10.1007/s10157-015-1209-9
State	Published - 2016/10/01

Keywords

Drug monitoring
Mizoribine
Pediatrics
Therapeutics

ASJC Scopus subject areas

Physiology
Nephrology
Physiology (medical)

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10.1007/s10157-015-1209-9

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Kaneda, H., Shimizu, M., Ohta, K., Ushijima, K., Gotoh, Y., Satomura, K., Nagai, T., Fujieda, M., Morooka, M., Yamada, T., Yamada, M., Wada, N., Takaai, M., Hashimoto, Y., & Uemura, O. (2016). Population pharmacokinetics of mizoribine in pediatric patients with kidney disease. Clinical and Experimental Nephrology, 20(5), 757-763. https://doi.org/10.1007/s10157-015-1209-9

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title = "Population pharmacokinetics of mizoribine in pediatric patients with kidney disease",

abstract = "Background: The present study aimed to obtain information enabling optimisation of the clinical effect of mizoribine (MZR) in pediatric patients with kidney disease. Methods: A total of 105 pediatric patients with kidney disease treated at our institutions were enrolled. Kidney transplant patients were excluded. Population pharmacokinetic analysis of MZR was performed based on serum concentration data. Area under the curve from time zero to infinity (AUC∞) and maximal concentration (Cmax) were calculated by Bayesian analysis. Results: In children, the appearance of MZR in the blood tended to be slower and the subsequent rise in blood concentration tended to be more sluggish, compared to healthy adults. Apparent volume of distribution and oral clearance were also higher in children compared to adults. A significant positive correlation was observed between patient age and AUC∞. There were significant differences of AUC∞ and Cmax by age group. No relationship was observed between the administration method of MZR and serum concentration. Conclusion: The pharmacokinetics of MZR was different in children compared to adults. To obtain the expected clinical efficacy, the regular MZR dosage schedule (2–3 mg/kg/day) might be insufficient for pediatric patients. In particular, younger patients might require a higher dosage of MZR per unit body weight.",

keywords = "Drug monitoring, Mizoribine, Pediatrics, Therapeutics",

author = "Hisashi Kaneda and Masaki Shimizu and Kazuhide Ohta and Katsumi Ushijima and Yoshimitsu Gotoh and Kenichi Satomura and Takuhito Nagai and Mikiya Fujieda and Masashi Morooka and Takuji Yamada and Masayoshi Yamada and Naohiro Wada and Mari Takaai and Yukiya Hashimoto and Osamu Uemura",

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doi = "10.1007/s10157-015-1209-9",

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Kaneda, H, Shimizu, M, Ohta, K, Ushijima, K, Gotoh, Y, Satomura, K, Nagai, T, Fujieda, M, Morooka, M, Yamada, T, Yamada, M, Wada, N, Takaai, M, Hashimoto, Y & Uemura, O 2016, 'Population pharmacokinetics of mizoribine in pediatric patients with kidney disease', Clinical and Experimental Nephrology, vol. 20, no. 5, pp. 757-763. https://doi.org/10.1007/s10157-015-1209-9

TY - JOUR

T1 - Population pharmacokinetics of mizoribine in pediatric patients with kidney disease

AU - Kaneda, Hisashi

AU - Shimizu, Masaki

AU - Ohta, Kazuhide

AU - Ushijima, Katsumi

AU - Gotoh, Yoshimitsu

AU - Satomura, Kenichi

AU - Nagai, Takuhito

AU - Fujieda, Mikiya

AU - Morooka, Masashi

AU - Yamada, Takuji

AU - Yamada, Masayoshi

AU - Wada, Naohiro

AU - Takaai, Mari

AU - Hashimoto, Yukiya

AU - Uemura, Osamu

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Background: The present study aimed to obtain information enabling optimisation of the clinical effect of mizoribine (MZR) in pediatric patients with kidney disease. Methods: A total of 105 pediatric patients with kidney disease treated at our institutions were enrolled. Kidney transplant patients were excluded. Population pharmacokinetic analysis of MZR was performed based on serum concentration data. Area under the curve from time zero to infinity (AUC∞) and maximal concentration (Cmax) were calculated by Bayesian analysis. Results: In children, the appearance of MZR in the blood tended to be slower and the subsequent rise in blood concentration tended to be more sluggish, compared to healthy adults. Apparent volume of distribution and oral clearance were also higher in children compared to adults. A significant positive correlation was observed between patient age and AUC∞. There were significant differences of AUC∞ and Cmax by age group. No relationship was observed between the administration method of MZR and serum concentration. Conclusion: The pharmacokinetics of MZR was different in children compared to adults. To obtain the expected clinical efficacy, the regular MZR dosage schedule (2–3 mg/kg/day) might be insufficient for pediatric patients. In particular, younger patients might require a higher dosage of MZR per unit body weight.

AB - Background: The present study aimed to obtain information enabling optimisation of the clinical effect of mizoribine (MZR) in pediatric patients with kidney disease. Methods: A total of 105 pediatric patients with kidney disease treated at our institutions were enrolled. Kidney transplant patients were excluded. Population pharmacokinetic analysis of MZR was performed based on serum concentration data. Area under the curve from time zero to infinity (AUC∞) and maximal concentration (Cmax) were calculated by Bayesian analysis. Results: In children, the appearance of MZR in the blood tended to be slower and the subsequent rise in blood concentration tended to be more sluggish, compared to healthy adults. Apparent volume of distribution and oral clearance were also higher in children compared to adults. A significant positive correlation was observed between patient age and AUC∞. There were significant differences of AUC∞ and Cmax by age group. No relationship was observed between the administration method of MZR and serum concentration. Conclusion: The pharmacokinetics of MZR was different in children compared to adults. To obtain the expected clinical efficacy, the regular MZR dosage schedule (2–3 mg/kg/day) might be insufficient for pediatric patients. In particular, younger patients might require a higher dosage of MZR per unit body weight.

KW - Drug monitoring

KW - Mizoribine

KW - Pediatrics

KW - Therapeutics

UR - http://www.scopus.com/inward/record.url?scp=84949517255&partnerID=8YFLogxK

U2 - 10.1007/s10157-015-1209-9

DO - 10.1007/s10157-015-1209-9

M3 - 学術論文

C2 - 26649561

AN - SCOPUS:84949517255

SN - 1342-1751

VL - 20

SP - 757

EP - 763

JO - Clinical and Experimental Nephrology

JF - Clinical and Experimental Nephrology

IS - 5

ER -

Population pharmacokinetics of mizoribine in pediatric patients with kidney disease

Abstract

Keywords

ASJC Scopus subject areas

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