Venkataramanan R, Habucky K, Burckart G J, Ptachcinski R J
School of Pharmacy, University of Pittsburgh, Pennsylvania.
Clin Pharmacokinet. 1989 Mar;16(3):134-61. doi: 10.2165/00003088-198916030-00002.
Diseases of the liver, kidney and heart influence the pharmacokinetics of several drugs. Organ transplantation is an accepted therapeutic option for the treatment of several disease states associated with these organs. Recently, there has been an increase in both graft and patient survival after transplantation of the liver, heart, kidney and bone marrow. Such patients normally receive a wide range of drugs, and optimisation of drug therapy requires a thorough understanding of the pharmacokinetics and pharmacodynamics of these drugs in transplant patients. However, only limited studies have been carried out to characterise drug kinetics in these situations. Available information indicates that drug kinetics cannot be considered normal in transplant patients. Drug absorption generally appears to be similar to that in healthy subjects. The plasma protein binding of drugs that primarily bind to albumin increases after transplantation, but remains lower than that observed in healthy subjects. While the binding of certain basic drugs may increase after transplantation due to an increase in the concentration of alpha 1-acid glycoprotein, a lower albumin concentration may mask this effect. Oxidative and conjugative metabolism as measured by the kinetics of antipyrine (phenazone) and paracetamol (acetaminophen) is normal, while the metabolism of steroids may be impaired. Serum creatinine does not appear to be a good indicator of the functional status of the kidney in transplant patients. It is also important to realise that there will be time-dependent changes in several kinetic parameters of drugs due to improvement in the physiological function from that associated with the disease state to that of the normal state. Individualisation and close monitoring of drug therapy is necessary in transplant patients.
肝脏、肾脏和心脏疾病会影响多种药物的药代动力学。器官移植是治疗与这些器官相关的多种疾病状态的一种公认的治疗选择。最近，肝脏、心脏、肾脏和骨髓移植后的移植物和患者存活率均有所提高。这类患者通常会使用多种药物，优化药物治疗需要全面了解这些药物在移植患者体内的药代动力学和药效学。然而，针对这些情况进行的药物动力学特征研究非常有限。现有信息表明，移植患者的药物动力学不能被视为正常。药物吸收通常似乎与健康受试者相似。主要与白蛋白结合的药物的血浆蛋白结合率在移植后会升高，但仍低于健康受试者。虽然某些碱性药物的结合可能会因α1-酸性糖蛋白浓度升高而在移植后增加，但较低的白蛋白浓度可能会掩盖这种效应。以安替比林（非那宗）和对乙酰氨基酚（扑热息痛）的动力学来衡量，氧化和结合代谢是正常的，而类固醇的代谢可能会受损。血清肌酐似乎不是移植患者肾脏功能状态的良好指标。还必须认识到，由于生理功能从疾病状态改善到正常状态，药物的几个动力学参数会随时间发生变化。移植患者需要进行个体化的药物治疗并密切监测。
