Pharmacokinetic and pharmacodynamic modeling for acute and chronic pain drug assessment

Introduction: Population pharmacokinetic and pharmacodynamic (PK/PD) modeling is a critical component of drug development. Quantitative PK/PD models are used in drug development to improve both the design and interpretation of clinical trials across therapeutic areas. Areas covered: In this review, the authors provide an overview of PK/PD modeling approaches and their applications in the management of acute and chronic pain as well as drug assessment. The advantages and limitations of these modeling approaches with regard to handling different end points of pain assessment in monotherapy and combination therapy are highlighted. Expert opinion: New modeling approaches suitable for analgesics used in treatment of acute and chronic pain have started to emerge during the past few years. The application of the clinical utility index is limited but highly encouraged in pain drug assessment as it may inform the optimal window for treatment of pain to attain the best benefit: risk ratio. Owing to the restricted range of pain scores, beta regression models and coarsening models may be more appropriate modeling approaches for the bounded outcome data, rather than regular nonlinear/linear models that assume normal or log-normal error distribution. Additionally, modeling of exposure-response in flexible chronic pain studies remains challenging, and further investigations are needed.