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Population Pharmacokinetics of Cyclosporine after Hematopoietic Stem Cell Transplantation in Pediatric Patients
Korean J Clin Pharm 2018;28(1):24-29
Published online March 31, 2018
© 2018 Korean College of Clinical Pharmacy.

So Yeon Cho1,2, Jeong Yee1, Wonku Kang3, Jae Youn Kim2, Sook Hee An*4, and Hye Sun Gwak*1

1College of pharmacy & Division of Life and Pharmaceutical Sciences, Seoul 03760, Republic of Korea
2Department of pharmacy, Asan Medical Center, Seoul 05505, Republic of Korea
3College of pharmacy, Chungang University, Seoul 06974, Republic of Korea
4College of pharmacy, Wonkwang University, Iksan 54538, Republic of Korea
Correspondence to: Hye Sun Gwak, College of Pharmacy & Division of Life and Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 05505, Republic of Korea
Tel: +82-2-3277-4376, Fax: +82-2-3277-2851
Sook Hee An, College of Pharmacy, Wonkwang University, 460 Iksandae-ro, Iksan-si, Jeonbuk 54538, Republic of Korea
Tel: +82-63-850-6821, Fax: +82-63-850-7309
Received December 16, 2017; Revised January 5, 2018; Accepted January 8, 2018.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background: Cyclosporine is an immunosuppressive agent used to treat and prevent graft versus host reaction (GVHR)−a complication associated with stem cell transplantation. This study aimed to develop a population pharmacokinetic model of cyclosporine and investigate factors affecting cyclosporine clearance in pediatric hematopoietic stem cell transplant patients.
Methods: A total of 650 cyclosporine concentrations recorded in 65 patients who underwent hematopoietic stem cell transplantation were used. Data including age, sex, weight, height, body surface area (BSA), type of disease, chemotherapy before stem cell transplantation, type of donor, serum creatinine levels, total bilirubin concentration, hematocrit value, and type of concomitant antifungal agents and methylprednisolone used were retrospectively collected. Data related to cyclosporine dosage, administration time, and blood concentration were also collected. All data were analyzed using the non-linear mixed effect model; a two-compartment model with first-order elimination was used.
Results: The population pharmacokinetic model of cyclosporine using the NONMEM program was as follows: CL (L/h) = 5.9 × (BSA / 1.2)0.9, V2 (L) = 54.5, Q (L/h) = 3.5, V3 (L) = 1080.0, ka (h-1) = 0.000377. BSA was selected as a covariate of cyclosporine clearance, which increased with an increase in BSA.
Conclusion: A population pharmacokinetic model for Korean pediatric hematopoietic stem cell transplant patients was developed, and the important factor affecting cyclosporine clearance was found to be BSA. The model might contribute to the development of the most appropriate dosing regimen for cyclosporine. Further studies on population pharmacokinetics should be carried out, prospectively targeting pediatric patients.
Keywords : Cyclosporine, stem cell transplantation, population pharmacokinetics, pediatrics

March 2018, 28 (1)
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