Clinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
Int J Clin Pharm. 2011 Dec;33(6):918-24. doi: 10.1007/s11096-011-9568-0. Epub 2011 Sep 29.
The effects of physiological changes in patients with obesity on pharmacokinetic parameters and the time course of drug response, especially in the field of haematology/oncology, are poorly understood. For some antimicrobial drugs, dosing considerations exist, while for cytostatic drugs, dose modifications for obese patients are not consistently recommended. Glomerular filtration rate and renal perfusion appear to be similar in obese and normal weight individuals, thus elimination of hydrophilic and extensively renally cleared drugs mainly depends upon creatinine clearance.
To provide information about drug dosing in morbidly obese patients undergoing allogenic haematopoietic stem cell transplantation and to develop dosing recommendations for those patients, based on literature data, pharmacokinetic properties and own experiences.
A review on the literature on drug dosing in obese patients as well as on the pharmacokinetic properties of drugs which are supposed to be used in the field of stem cell transplantation was combined with own data on drug dosing and pharmacokinetic drug monitoring in a morbidly obese patient undergoing matched-unrelated allogenic peripheral blood stem cell transplantation.
For hydrophilic and extensively renally cleared drugs (e.g. piperacillin/sulbactam, cotrimoxazole, fludarabine) standard dosages for adult patients or dosing based on ideal body weight (IBW) (e.g. aciclovir, methotrexate) can be used. For ciclosporin and digitoxin we could show that high initial doses are needed to achieve sufficient plasma concentrations. After steady state distribution was completed, maintenance doses comparable to normal weight patients are sufficient. Likewise, distribution of enoxaparin and phenytoin seems to take longer in obese patients. Dosing recommendations of 25 drugs that can be used in morbidly obese patients undergoing allogenic stem cell transplantation are given.
Pharmacotherapy in morbidly obese patients undergoing allogenic stem cell transplantation is possible, if pharmacokinetic properties of the drugs are considered and close monitoring of plasma concentrations is performed.
肥胖患者的生理变化对药代动力学参数和药物反应时间进程的影响，尤其是在血液学/肿瘤学领域，尚未得到充分理解。对于某些抗菌药物，存在剂量考虑因素，而对于细胞毒性药物，肥胖患者的剂量调整并不总是被推荐。肥胖和正常体重个体的肾小球滤过率和肾灌注似乎相似，因此亲水性和广泛肾脏清除的药物的消除主要取决于肌酐清除率。
提供有关接受同种异体造血干细胞移植的病态肥胖患者药物剂量的信息，并根据文献数据、药代动力学特性和自身经验，为这些患者制定剂量建议。
对肥胖患者药物剂量的文献综述，以及假定在干细胞移植领域使用的药物的药代动力学特性，结合我们在接受匹配非亲缘外周血造血干细胞移植的病态肥胖患者中药物剂量和药代动力学药物监测的数据进行了综合分析。
对于亲水性和广泛肾脏清除的药物（如哌拉西林/舒巴坦、复方磺胺甲噁唑、氟达拉滨），可以使用成人患者的标准剂量或基于理想体重（IBW）的剂量（如阿昔洛韦、甲氨蝶呤）。对于环孢素和地高辛，我们证明需要高初始剂量才能达到足够的血浆浓度。达到稳定状态分布后，维持剂量与正常体重患者相当即可。同样，肥胖患者中依诺肝素和苯妥英的分布似乎需要更长的时间。给出了 25 种可用于病态肥胖患者接受同种异体干细胞移植的药物的剂量建议。
如果考虑药物的药代动力学特性并进行密切的血浆浓度监测，则可以对接受同种异体干细胞移植的病态肥胖患者进行药物治疗。
