Journal of Pharmacokinetics and Pharmacodynamics

, Volume 38, Issue 4, pp 433–447

Optimal study design for pioglitazone in septic pediatric patients

  • Catherine M. T. Sherwin
  • Lili Ding
  • Jennifer Kaplan
  • Michael G. Spigarelli
  • Alexander A. Vinks
Article

DOI: 10.1007/s10928-011-9202-8

Cite this article as:
Sherwin, C.M.T., Ding, L., Kaplan, J. et al. J Pharmacokinet Pharmacodyn (2011) 38: 433. doi:10.1007/s10928-011-9202-8

Abstract

The objective was to demonstrate the methodology and process of optimal sparse sampling pharmacokinetics (PK). This utilized a single daily dose of pioglitazone for pediatric patients with severe sepsis and septic shock based upon adult and minimal adolescent data. Pioglitazone pharmacokinetics were modeled using non-compartment analysis WinNonlin Pro (version 5.1) and population kinetics using NONMEM (version 7.1) with first order conditional estimation method (FOCE) with interaction. The initial model was generated from single- and multiple-dose pioglitazone PK data (15 mg, 30 mg, and 45 mg) in 36 adolescents with diabetes. PK models were simulated and overlaid upon original data to provide a comparison best described by a single compartment, first order model. The optimal design was based on the simulated oral administration of pioglitazone to three groups of pediatric patients, age 3.8 (2–6 years), weight 14.4 (7–28 kg); age 9.6 (6.1–11.9 years), weight 36.5 (28.1–48 kg) and age 15.5 (12–17 years,) weight 61.6 (48.1–80 kg). PFIM (version 3.2) was used to evaluate sample study size. Datasets were compiled using simulation for each dose (15, 30 and 45 mg) for the potential age/weight groups. A target dose of 15 mg daily in the youngest and middle groups was considered appropriate with area under the curve exposure levels (AUC) comparable to studies in adolescents. The final optimal design suggested time points of 0.5, 2, 6 and 21 h for 24 h dosing. This methodology provides a robust method of utilizing adult and limited adolescent data to simulate allometrically scaled, pediatric data sets that allow the optimal design of a pediatric trial. The pharmacokinetics of pioglitazone were described adequately and simulated data estimates were comparable to literature values. The optimal design provided clinically attainable sample times and windows.

Keywords

Optimal design Pediatric Pioglitazone Sepsis Sparse sampling 

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Catherine M. T. Sherwin
    • 1
    • 6
  • Lili Ding
    • 2
  • Jennifer Kaplan
    • 3
    • 5
  • Michael G. Spigarelli
    • 1
    • 4
    • 5
  • Alexander A. Vinks
    • 1
    • 5
  1. 1.Division of Clinical PharmacologyCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  2. 2.Division of Biostatistics and EpidemiologyCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  3. 3.Division of Critical Care MedicineCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  4. 4.Clinical Trials OfficeCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  5. 5.Department of PediatricsCollege of Medicine, University of CincinnatiCincinnatiUSA
  6. 6.Division of Clinical Pharmacology and Clinical Trials Office, Department of PediatricsUniversity of Utah School of MedicineSalt Lake CityUSA

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