Population pharmacodynamic modeling of exenatide after 2-week treatment in STZ/NA Diabetic rats

Ting Chen, Leonid Kagan, Donald E. Mager

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The purpose of this study is to investigate the effect of exenatide on glycemic control following two administration routes in a streptozotocin/nicotinamide (STZ/NA)-induced diabetic rat model, and to develop a pharmacodynamic model to better understand the disease progression and the action of exenatide in this experimental system. Two groups of STZ/NA-induced diabetic rats were treated for 2 weeks with 20 (μg/kg/day) of exenatide, either by continuous subcutaneous (SC) infusion or two SC injections daily. Disease progression was associated with slower glucose utilization. Fasting blood glucose was significantly reduced by 30 mg/dL in both treatment groups at the end of 2 weeks. A subsequent intravenous glucose tolerance test (IVGTT) confirmed an improved glucose tolerance in both treatment groups; however, overall glycemic control was similar between groups, likely due to the relatively low and short-term drug exposure. A population indirect response model was successfully developed to simultaneously describe the STZ/NA-induced disease progression, responses to an IVGTT, and exenatide effects on these systemic challenges. The unified model includes a single set of parameters, and the cumulative area under the drug-receptor concentration curve was used as a unique driving force to account for systemic effects long after drug elimination.

Original languageEnglish (US)
Pages (from-to)3844-3851
Number of pages8
JournalJournal of Pharmaceutical Sciences
Volume102
Issue number10
DOIs
StatePublished - Oct 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Keywords

  • Exenatide
  • Mathematical modeling
  • Pharmacodynamics
  • Pharmacokinetics
  • Type 2 diabetes

Fingerprint

Dive into the research topics of 'Population pharmacodynamic modeling of exenatide after 2-week treatment in STZ/NA Diabetic rats'. Together they form a unique fingerprint.

Cite this