Pharmacokinetics and pharmacodynamics of glimepiride polymorphs

Int J Pharm. 2018 Dec 20;553(1-2):272-280. doi: 10.1016/j.ijpharm.2018.10.050. Epub 2018 Oct 23.


Glimepiride (GLIM) is used as an oral antihyperglycemic agent for treatment of type 2 diabetes. The drug presents two polymorphic forms (GLIM form I and GLIM form II) described in the literature, and according to in vitro data, GLIM form II is about 3.5 times more soluble and releases 2 times the drug amount than GLIM form I in the physiological pH range. Considering the literature in vitro data and that the diabetes treatment demands glycemic control, avoiding abrupt fluctuations in the blood glucose levels, this work aimed to study the impact of GLIM polymorphism in the in vivo performance of GLIM solid oral dosages. For this, hard gelatin capsules with GLIM form I or II were prepared and orally administered in rats. After that, pharmacokinetic studies were performed by sampling animal blood at different times, and biochemical parameters (pharmacodynamic), such as glucose and insulin, were also evaluated. Our results showed that the in vitro data corroborate with our in vivo assays. GLIM form II provided higher plasma concentration of drug than form I (at baseline up to approximately 200 min after oral administration) and, consequently, increased insulin release and reduced levels of glucose, showing good correlation between pharmacokinetic and pharmacodynamics assays. Thus, this study demonstrated that GLIM polymorphs in oral dosages might alter the drug efficacy, which may expose the patients to risks, such as hypoglycemia.

Keywords: Glimepiride; In vivo studies; Pharmacodynamics; Pharmacokinetics; Polymorphism; Solid-state; Type 2 diabetes.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Blood Glucose / drug effects*
  • Capsules
  • Crystallization
  • Gelatin
  • Hypoglycemic Agents / chemistry*
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / pharmacology
  • Insulin / blood*
  • Male
  • Rats
  • Rats, Wistar
  • Solubility
  • Sulfonylurea Compounds / chemistry*
  • Sulfonylurea Compounds / pharmacokinetics
  • Sulfonylurea Compounds / pharmacology


  • Blood Glucose
  • Capsules
  • Hypoglycemic Agents
  • Insulin
  • Sulfonylurea Compounds
  • glimepiride
  • Gelatin