Population Modeling Is a Critical Element of Bridging Pharmacokinetic Data From Dried Blood Spot and Plasma Across Clinical Programs

Authors: Dockendorf M, Li CC, Kowalski K, Yang B, Ma L, Kleijn H, Bosch R, Forman M, Marcantonio G, Voss T, Jaworowicz DJ, Passarell JA, Bateman K, Stone J, Kothare PA
Conference: AAPS
Keywords: DBS:plasma, pharmacokinetic, PK, PKPD methodology
Division: Cognigen

Abstract

Purpose: To demonstrate through two case studies how population pharmacokinetic (PK) modeling should be leveraged for bridging plasma and dried blood spot (DBS) PK data across clinical development programs.

Methods: In two case studies (MK-X and MK-Y), population PK models initially developed from Ph1 plasma data were updated to include plasma and DBS data from healthy subjects (Phase 1 setting) and patient (late-stage trials) plasma- DBS bridging studies. DBS samples were collected via in-clinic venipuncture (MK-X and MK-Y) and in-clinic and at-home fingerstick (MK-Y). An estimated population slope converted between DBS and plasma concentrations. Separate residual errors for plasma and DBS data were estimated. For MK-Y, residual error was further partitioned based on in-clinic vs at-home DBS sampling. Models were qualified through standard diagnostics and qualification approaches. Interchangeability of matrices was evaluated through various approaches including a comparison of post-hoc predicted exposures

American Association of Pharmaceutical Scientists (AAPS), November 2 – 6, 2014, San Diego, CA

By M. Dockendorf, CC Li, K. Kowalski, B. Yang, L. Ma, H. Kleijn, R. Bosch, M. Forman, G. Marcantonio, T Voss, David Jaworowicz Jr, Julie Passarell, K Bateman, J Stone, P Kothare