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Models for Plasma Glucose, HbA1c, and Hemoglobin Interrelationships in Patients with Type 2 Diabetes Following Tesaglitazar Treatment
Author(s) -
Hamrén B,
Björk E,
Sunzel M,
Karlsson MO
Publication year - 2008
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2008.2
Subject(s) - hemoglobin , pharmacodynamics , pharmacokinetics , agonist , medicine , endocrinology , pharmacology , type 2 diabetes , potency , diabetes mellitus , plasma glucose , chemistry , receptor , in vitro , biochemistry
Pharmacokinetic (PK) pharmacodynamic (PD) modeling was applied to understand and quantitate the interplay between tesaglitazar (a peroxisome proliferator–activated receptor α/γ agonist) exposure, fasting plasma glucose (FPG), hemoglobin (Hb), and glycosylated hemoglobin (HbA1c) in type 2 diabetic patients. Data originated from a 12‐week dose‐ranging study with tesaglitazar. The primary objective was to develop a mechanism‐based PD model for the FPG–HbA1c relationship. The secondary objective was to investigate possible mechanisms for the tesaglitazar effect on Hb. Following initiation of tesaglitazar therapy, time to new FPG steady state was ~9 weeks, and tesaglitazar potency in females was twice that in males. The model included aging of red blood cells (RBCs) using a transit compartment approach. The RBC life span was estimated to 135 days. The transformation from RBC to HbA1c was modeled as an FPG‐dependent process. The model indicated that the tesaglitazar effect on Hb was caused by hemodilution of RBCs. Clinical Pharmacology & Therapeutics (2008); 84 , 2, 228–235 doi: 10.1038/clpt.2008.2