Department of Bioengineering and Therapeutic Sciences, Schools of Pharmacy and Medicine, University of California San Francisco, 533 Parnassus Avenue, Room U-68, UCSF Box 0912, San Francisco, California, 94143, USA.
AAPS J. 2019 Sep 3;21(6):103. doi: 10.1208/s12248-019-0373-3.
The emergence and continued evolution of the transporter field has caused re-evaluation and refinement of the original principles surrounding drug disposition. In this paper, we emphasize the impact that transporters can have on volume of distribution and how this can affect the other major pharmacokinetic parameters. When metabolic drug-drug interactions or pharmacogenomic variance changes the metabolism of a drug, the volume of distribution appears to be unchanged while clearance, bioavailability, and half-life are changed. When transporters are involved in the drug-drug interactions or pharmacogenomic variance, the volume of distribution can be markedly affected causing counterintuitive changes in half-life. Cases are examined where a volume of distribution change is significant enough that although clearance decreases, half-life decreases. Thus, drug dosing decisions must be made based on CL/F changes, not half-life changes, as such volume of distribution alterations will also influence the half-life results.
转运体领域的出现和持续发展促使人们重新评估和完善了药物处置的原始原则。在本文中，我们强调了转运体对分布容积的影响，以及这如何影响其他主要的药代动力学参数。当代谢性药物相互作用或药物基因组学变异改变药物的代谢时，表观分布容积似乎保持不变，而清除率、生物利用度和半衰期发生改变。当转运体参与药物相互作用或药物基因组学变异时，分布容积会受到显著影响，导致半衰期发生反直觉的变化。我们检查了一些情况，其中分布容积的变化非常显著，尽管清除率降低，但半衰期也降低。因此，药物剂量决策必须基于 CL/F 的变化做出，而不是半衰期的变化，因为这种分布容积的改变也会影响半衰期的结果。
