Korean Journal of Clinical Pharmacy (한국임상약학회지)

Korean College Of Clinical Pharmacy (한국임상약학회)
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Population Pharmacokinetics of Cyclosporine after Hematopoietic Stem Cell Transplantation in Pediatric Patients

조혈모세포 이식을 받은 소아 환자에서 cyclosporine의 집단 약동학 분석

  • Cho, So Yeon (College of pharmacy & Division of Life and Pharmaceutical Sciences) ;
  • Kang, Wonku (College of pharmacy, Chungang University) ;
  • Yee, Jeong (College of pharmacy & Division of Life and Pharmaceutical Sciences) ;
  • Kim, Jae Youn (Department of pharmacy, Asan Medical Center) ;
  • An, Sook Hee (College of pharmacy, Wonkwang University) ;
  • Gwak, Hye Sun (College of pharmacy & Division of Life and Pharmaceutical Sciences)
  • 조소연 (이화여자대학교 약학대학) ;
  • 강원구 (중앙대학교 약학대학) ;
  • 이정 (이화여자대학교 약학대학) ;
  • 김재연 (서울아산병원 약제팀) ;
  • 안숙희 (원광대학교 약학대학) ;
  • 곽혜선 (이화여자대학교 약학대학)
  • Received : 2017.12.16
  • Accepted : 2018.01.08
  • Published : 2018.03.02
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Abstract

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 anti-fungal 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: $CL(L/h)=5.9{\times}(BSA/1.2)^{0.9}$, V2 (L) = 54.5, Q (L/h) = 3.5, V3 (L) = 1080.0, $k_a(h^{-1})=0.000377$. 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

References

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