1a.Department of Pharmacy, b.Department of Hematology Fujian Medical University Union Hospital, Fuzhou 350001, China; 2.Fujian Institute for Food and Drug Outity Control, Fuzhou 350001, China
ժҪĿ�� ��������������(limited sampling strategy, LSS)���ڹ�����Ѫ��ϸ����ֲ(hematopoietic stem cell transplantation,HSCT)���߾�����ע������(busulfan,Bu)���ҩ-ʱ�������(an area under the plasma concentration versus time curve,AUC)������ 22����Ѫ��ϸ����ֲ���߾�����ע��������,�ɼ�����ʱ���Ѫ����Ʒ,��LC-MS/MS�ⶨ������ѪҩŨ��,�þ��䷽������ҩ��ѧ����������ϡ��ѪҩŨ�����ݵ㽨����Ԫ�ع���ѧģ��,����AUC0-6,����ģ�ͽ�����֤��ͨ���������ϵ��(intraclass correlation coefficient,ICC)��Bland-Altman (BA)�����������䷨��������������һ���ԡ���� ����(C2��C5)Ԥ���ҩ��ѧ�����ع�ģ�͵����Թ�ϵ�Ϻ�(������r2=0.917),ƽ��Ԥ�����Ϊ0.20%,���������Ϊ4.48%,�������ϵ����95%��������Ϊ0.914~0.984,BA����һ���Խ���Ϊ-0.9~8.8���뾭�䷨���۽��һ�¡����� C2��C5����AUC0-6���������������ڰ��������ٴ�ѪҩŨ�ȼ�⡣
Abstract��OBJECTIVE To establish limited sampling strategy to estimate area under the curve (AUC) of HSCT patients who had received busulfan (Bu) intravenous infusion. METHODS Plasma samples were collected at certain time points from 22 HSCT patients who had received busulfan intravenous infusion. The LC-MS/MS method was used to measure blood concentration of busulfan. The classical method was used to calculate pharmacokinetic parameters. To estimate AUC0-6, measured blood concentration data was used to build a multiple linear regression model which was subsequently validated. Consistency between results produced by the traditional method and the proposed LSS respectively was assessed by the intraclass correlation coefficient (ICC) and Bland-Altman (BA) analysis. RESULTS It is shown that model based on concentrations on two sampling time points (2 and 5 h) is able to predict AUC0-6accurately (adjusted r2=0.917. MPE=0.2%, RMSE=4.48%). The 95% confidence interval of ICC is 0.914-0.984 while the limit of agreement in the BA is -0.9-8.8. Results produced by limited sampling strategy are nearly consistent with AUC0-6 produced by the classical method. CONCLUSION The proposed limited sampling strategy to estimate AUC0-6 based on C2 and C5 can be used to busulfan blood concentration monitoring in clinical practice.
ZHENG P,LIU S T,LI C F,et al. Pharmacokinetics of bufulfan in pediatric and adult patients prior to hematopoietic stem cell transplantation.Chin Pharm J(�й�ҩѧ��־),2013,48(13):1088-1093.
[2]
HASSAN B M,LJUNGMAN P,BOLME P,et al.Busulfan bioavailability.Blood,1994,84(7):2144-2150.
[3]
MCCUNE J S,GIBBS J P,SLANERY J T.Plasma concentration monitoring of busulfan:Does it improve clinical outcome .Clin Pharmacokinet,2000,39(2):155-164.
[4]
HOFFER E,AKRIA L,ACHERB I,et al.A simple approximationfor busulfan dose adjustment in adult patient undergoing bonemarrow transplantation.Ther Drug Monit,2004,26 (3):33l-335.
[5]
ANDERSSON B S,KASHYAP A,GIAN V,et al. Conditioningtherapy withintravenous busu1fan and cyclophosphamide(IVBuCy2)for hematologic malignancies prior to allogeneic stemce1l transplantation:A phase II study.Biol Blood Marrow Transplant,2002,8(3):l45-154.
[6]
ANDERSSON B S,MADDEN T,TRAN H T,et al. Acute safety andpharmacokinetics of intravenous busulfan when used with oral busulfan and cyclophosphamide as pre-transplantation conditioning therapy:A phase I study. Biol Blood Marrow Transplant,2000,6(5):548-554.
[7]
DUPUIS L L, CATBRYN S, TAL S, et al. IV Busulfan dose individualization in children under going hematopoietic stem cell transplant:Limited sampling strategies. Bio Blood Marrow Transplant, 2008, 14(5):576-582.
[8]
XU G.Jackknife estimation and its application .J Shandong Normal Univ(ɽ��ʦ����ѧѧ��),2000,15:454-455.
[9]
EFRON B. Bootstrap methods:Another look at the Jackknife. Annals Stat,1979,7(1):1-12.
[10]
BAO H C. A new way to reduce the standard deviation of the random errors-��Jackknife��.J Staff Worker��s Univ(ְ��ѧ��),2004,2:18-21.
[11]
XU L,LV Y H,YANG J,et al. Prediction of the AUC and the comparison of approaches for validation.Chin J Clin Pharmacol Ther(�й��ٴ�ҩ��ѧ������ѧ),2007,12(9):1062-1067.
[12]
ZHOU Y H, XU J F, HE J, et al. Evaluation and application on different assessment methods of consistency of diagnostic test. Chin J Health Statist(�й�����ͳ��ѧ),2011,28(1):41-42.
2015, Vol. 50 
