Am J Pharmacol | Volume 8, Issue 1 | Research Article | Open Access
Domina Petrić
Department of Emergency, University Hospital Center Split, Croatia
*Correspondance to: Domina Petrić
Fulltext PDFImmune Checkpoint Inhibitors (ICIs) have revolutionized oncology, yet their high cost, narrow therapeutic window, and substantial inter-individual pharmacokinetic variability limit optimal therapeutic outcomes. Recent evidence indicates that patients who respond to anti-PD-1 and anti-CTLA-4 therapy exhibit a marked, time-dependent reduction in drug clearance, leading to supratherapeutic exposure at fixed-dose regimens. This technical report presents a population pharmacokinetic model for individualized ICI dosing that integrates baseline covariates (body weight, serum albumin, biological sex) with dynamic clearance changes stratified by responder status. The model predicts that responders achieve steady-state clearance reductions of approximately 35% compared to 10% in non-responders, enabling dose reductions of up to 28% while maintaining target exposure. Simulations across a heterogeneous cohort demonstrate mean drug savings of 13.6%, with 42% of patients achieving >20% dose reduction. These findings support the integration of therapeutic drug monitoring, in silico pharmacokinetic modeling, and response-adaptive dosing into clinical practice to reduce toxicity burden and treatment costs without compromising efficacy.
Immune checkpoint inhibitors; Pharmacokinetics; Individualized dosing; Population PK model; Therapeutic drug monitoring; Precision oncology
Domina P. Individualized Dosing of Immune Checkpoint Inhibitors a Population Pharmacokinetic Model for Responder-Stratified Therapy. Am J Pharmacol. 2026; 8(1): 1041.