Korean Journal of Clinical Pharmacy (한국임상약학회지)

Korean College Of Clinical Pharmacy (한국임상약학회)
권호 표지

Pharmacodynamic Modeling of Vincristine in Lymphoma Patients

림프종 환자에서 회귀모형을 이용한 vincristine의 약물 용량 예측 인자 및 부작용 모델 연구

  • Seo, Jeong-Won (New Drug Research Team, National Institute of Food and Drug Safety Evaluation (NIFDA)) ;
  • Kim, Dong-Hyun (College of Pharmacy, Chungnam National University) ;
  • Yun, Jin-Sang (Chungnam National University Hospital) ;
  • Kim, Seon-Hwa (Division of Pharmacological Reserch, National institute of Food and Drug Evaluation, Korea Food & Drug Evaluation) ;
  • Choi, Bo-Yoon (College of Pharmacy, Seoul National University) ;
  • Oh, Jung-Mi (College of Pharmacy, Seoul National University) ;
  • Kwon, Kwang-Il (College of Pharmacy, Chungnam National University)
  • 서정원 (식품의약품안전평가원 의료제품연구부 신약연구팀) ;
  • 김동현 (충남대학교 약학대학) ;
  • 윤진상 (충남대학교병원 진단검사의학과) ;
  • 김선화 (식품의약품안전평가원 약리연구과) ;
  • 최보윤 (서울대학교 약학대학) ;
  • 오정미 (서울대학교 약학대학) ;
  • 권광일 (충남대학교 약학대학)
  • Received : 2011.02.23
  • Accepted : 2011.05.14
  • Published : 2011.06.30
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Abstract

The objective of this study was to determine whether any pretreatment parameters were associated with pharmacological effect or toxicity parameters after vincristine administration and to describe a mathematical model, which explains the interpatient pharmacodynamic variability. The relationship between patient characteristics and vincristine dose and hematological toxicity were evaluated. 68 pediatric and adolescence patients and 107 adults with acute lymphoblastic leukemia were treated with vincristine $1.5mg/m^2/day$ IV and other anticancer drugs as scheduled. Complete blood counts and other blood test results were obtained. The input variables were age, gender, weight, lean body weight (LBW), height, body surface area, vincristine dose and total vincristine dose. The outcome measures were nadir values (white blood cells, absolute neutrophil counts, hemoglobin, and platelets); the absolute decrease, relative decrease, and survival fraction of blood cells. Polynomial regression analysis was carried out to determine the other significant covariates. The variability of $WBC_{nadir}$ was modeled with good precision and accuracy with a two-covariate model. This model should be validated and improved on with further clinical data. We believe that such pharmacodynamic modeling should be explored further to determine its performance and clinical relevance compared with modeling using pharmacokinetic parameter.

Keywords

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