title: Pharmacokinetic-pharmacodynamic model of the antihypertensive interaction between telmisartan and hydrochlorothiazide in spontaneously hypertensive rats.
abstract: OBJECTIVE
  The goal of this study was to establish an integrated indirect response pharmacokinetic-pharmacodynamic model between telmisartan and hydrochlorothiazide to describe the antihypertensive interaction of these two drugs in spontaneously hypertensive rats.
  
  
  METHODS
  The blood pressure and plasma concentrations were measured by the tail-cuff test and high performance liquid chromatography-mass spectrometry, respectively, in spontaneously hypertensive rats. The current pharmacokinetic-pharmacodynamic model was based on the non-competitive pharmacodynamic interaction of two drugs acting on different physiological processes.
  
  
  RESULTS
  This model was able to acquire the temporal changes in drug concentration and blood pressure after administration of telmisartan or hydrochlorothiazide. The noncompetitive pharmacodynamic interaction assumed that the decreased blood pressure was attributed to the inhibitory function of telmisartan and stimulatory function of hydrochlorothiazide after administration of these two drugs. There was no significant pharmacokinetic change of telmisartan and hydrochlorothiazide in the different groups tested. The model predicted a synergistic pharmacodynamic interaction when telmisartan was administered in combination with hydrochlorothiazide, which was notably stronger than if the effects were additive.
  
  
  CONCLUSIONS
  The results showed that the presented pharmacokinetic-pharmacodynamic model was suitable for describing the antihypertensive interaction between telmisartan and hydrochlorothiazide.
authors.affiliation: State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Hao
authors.forename: Yuancheng
authors.initials: Y
authors.lastname: Chen
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhao
authors.forename: Xiaoquan
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001562:Benzimidazoles / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001565:Benzoates / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions / Q000502:physiology*; D004359:Drug Therapy, Combination / Q000379:methods; D006852:Hydrochlorothiazide / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D000077333:Telmisartan
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D006852:Hydrochlorothiazide; D000077333:Telmisartan
keywords: biopharmaceutics and drug disposition; pharmacokinetics and drug disposition