Pharmacokinetic Drug Interactions in Solid Organ Transplantation: From Molecular Mechanisms and Formulation Science to Therapeutic Drug Monitoring and Precision Dosing

Solid organ transplant (SOT) recipients are especially vulnerable to pharmacokinetic drug interactions because narrow-therapeutic-index immunosuppressants are used in the setting of polypharmacy, rapidly changing physiology, variable gastrointestinal function, and frequent anti-infective therapy. Interaction magnitude is rarely determined by the perpetrator drug alone; formulation, genotype, hematocrit, albumin, organ function, inflammation, and time after transplantation can materially change the observed exposure response. This narrative review integrates mechanistic and clinical evidence across desensitization, induction, maintenance immunosuppression, and rejection treatment. Particular attention is given to cytochrome P450 3A (CYP3A)- and transporter-mediated interactions, mycophenolic acid enterohepatic recirculation, formulation-dependent exposure, drug–drug–gene interactions, food and herbal products, physiological modifiers, interaction-informed therapeutic drug monitoring, and model-informed dosing. Quantitative transplant data are prioritized where available, with non-SOT evidence identified when it materially informs mechanism or management. A practical 6-D framework (Drug, Dose, Determinants, Drug interactions, Data, and Decision) is proposed to organize patient-specific assessment and move interaction management beyond binary alerts toward quantitative, concentration-guided precision dosing.