Will Pig Organ Xenotransplantation in Patients Complicate the Use of Commonly Administered Drugs?

Abstract

Recent advances in gene-edited pig organ xenotransplantation offer a promising solution to the critical shortage of human donor organs. Differences in physiology, drug metabolism, excretion, and responses between species require careful consideration for posttransplant medication management in human recipients. This brief review compares the anatomical, physiological, and biochemical features of pig and human organs, particularly in relation to the liver, kidney, heart, and lungs, and their potential implications on drug exposure, response, and efficacy after xenotransplantation. The transplantation of gene-edited organs from pigs to humans will result in a complex metabolic interplay, depending on the organ being transplanted. For example, if a pig liver is transplanted into a human, the drugs metabolized by the pig liver may be excreted in the bile or by the human kidney. There may be breed-specific metabolism of drugs, and genetic polymorphism in pigs may contribute to variability in drug exposure similar to what is observed among humans. Furthermore, there may be significant size differences between pigs and human organs, and their functional capabilities may change over time as the pig organs age within the recipient's body. In this article, we review how pig organ xenotransplantation may impact physiology, drug exposure, and response to immunosuppressive agents, anti-infective drugs, and other medications commonly used for posttransplant medical conditions. There is limited data available on the specific breeds of pigs used in xenotransplantation, and further research is required to ensure appropriate drug dosing, minimize toxicity, and optimize long-term graft function in recipients of pig organ xenografts.