Models for plasma glucose, HbA1c, and hemoglobin interrelationships in patients with type 2 diabetes following tesaglitazar treatment

• Published in: Clinical pharmacology and therapeutics Vol. 84; no. 2; p. 228
• Main Authors: Hamrén, B, Björk, E, Sunzel, M, Karlsson, Mo
• Format: Journal Article
• Language: English
• Published: United States 01.08.2008
• Subjects: Adult; Aged; Aged, 80 and over; Alkanesulfonates - therapeutic use; Biomarkers - blood; Blood Glucose - metabolism; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Fasting; Female; Glycated Hemoglobin A - metabolism; Hemodilution; Hemoglobins - metabolism; Humans; Hypoglycemic Agents - therapeutic use; Male; Middle Aged; Phenylpropionates - therapeutic use; PPAR alpha - agonists; PPAR gamma - agonists
• ISSN: 1532-6535
• DOI: 10.1038/clpt.2008.2

Pharmacokinetic (PK) pharmacodynamic (PD) modeling was applied to understand and quantitate the interplay between tesaglitazar (a peroxisome proliferator-activated receptor alpha/gamma 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 approximately 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.