A Regulatory Perspective on Pharmacokinetic/Pharmacodynamic Modelling

The document from 1999 provides an overview of pharmacokinetic/pharmacodynamic (PK/PD) modeling, emphasizing its role in drug development and regulation. It discusses parameter estimation methods, particularly the two-stage method and likelihood-based methods, and the use of NONMEM software. The paper includes a study on tamsulosin in 374 patients for PK analysis and 579 patients for PD analysis, concluding that a 0.4 mg daily dose is optimal for improving peak urine flow in benign prostatic hypertrophy (BPH) patients. It also covers a study on piroxicam and its complex in 48 subjects, finding significant analgesic effects at 20 and 40 mg doses with no difference in efficacy between the doses. Additionally, a study on minoxidil involving 41 subjects addressed safety concerns, showing a dose-related increase in heart rate but no significant covariate effects on its pharmacodynamics. The document highlights the utility of PK/PD modeling in determining drug efficacy and safety, informing dosing recommendations, and its critical role in regulatory decision-making.