Influence of Single and Multi Dose Treatment of Glipizide on Pharmacokinetics and Pharmacodynamics of Irbesartan in Normal and Hypertensive Rats

High Blood Press Cardiovasc Prev. 2017 Jun;24(2):179-185. doi: 10.1007/s40292-017-0195-2. Epub 2017 Apr 6.

Abstract

Purpose: The present study was carried out to investigate the pharmacokinetic and pharmacodynamic drug interaction of irbesartan with glipizide after single and multi dose treatment in normal and hypertensive rat models to evaluate the safety and effectiveness of the combination.

Methods: The study was conducted on normal and 10% fructose solution induced hypertensive rats. Irbesartan and glipizide were administered orally for 7 days and on 8th day blood samples were collected for 12 h at regular time intervals from irbesartan alone and in combination with glipizide treated groups. The blood samples were analyzed for various pharmacokinetic and pharmacodynamic parameters.

Results: Irbesartan caused marked reduction in blood pressure in hypertensive rats. The combination of irbesartan and glipizide in hypertensive rats produce significant change in blood pressure (pharmacodynamic) and also significance in pharmacokinetic parameters of irbesartan with glipizide in single dose and multiple doses.

Conclusion: The results of present study demonstrated that the synergistic activity of irbesartan with glipizide was observed.

Keywords: Antihypertensive activity; Glipizide; Irbesartan; Pharmacodynamic; Pharmacokinetic.

MeSH terms

  • Administration, Oral
  • Angiotensin II Type 1 Receptor Blockers / administration & dosage
  • Angiotensin II Type 1 Receptor Blockers / pharmacokinetics*
  • Animals
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / pharmacokinetics*
  • Biological Availability
  • Biphenyl Compounds / administration & dosage
  • Biphenyl Compounds / pharmacokinetics*
  • Blood Pressure / drug effects*
  • Cytochrome P-450 Enzyme System / metabolism
  • Disease Models, Animal
  • Drug Administration Schedule
  • Drug Interactions
  • Fructose
  • Glipizide / administration & dosage*
  • Glipizide / pharmacokinetics
  • Hypertension / blood
  • Hypertension / chemically induced
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / pharmacokinetics
  • Irbesartan
  • Male
  • Rats, Wistar
  • Tetrazoles / administration & dosage
  • Tetrazoles / pharmacokinetics*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Antihypertensive Agents
  • Biphenyl Compounds
  • Hypoglycemic Agents
  • Tetrazoles
  • Fructose
  • Cytochrome P-450 Enzyme System
  • CYP2C9 protein, rat
  • Irbesartan
  • Glipizide