Pharmacokinetic-pharmacodynamic profile of angiotensin II receptor antagonists.
The pharmacokinetic and pharmacodynamic properties of nonpeptide angiotensin antagonists in humans are reviewed in this paper. Representatives of this new therapeutic class share common features: lipophilia, intermediate bioavailability, high affinity for plasma proteins and liver metabolism; some have active metabolites. Angiotensin II antagonists block the blood pressure response to exogenous angiotensin II in healthy volunteers, decrease baseline blood pressure in both normal and hypertensive patients, produce a marked rise in plasma renin activity and endogenous angiotensin II and increase renal blood flow without altering glomerular filtration rate. These effects are dose-dependent, but their time course varies between the drugs owing to pharmacokinetic and pharmacodynamic differences. Additionally, the extent of blood pressure reduction is dependent on physiological factors such as sodium and water balance. The characterisation of their pharmacokinetic-pharmacodynamic relationships deserves further refinement for designing optimal therapeutic regimens and proposing dosage adaptations in specific conditions.
Csajka
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Département de Médecine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
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Brunner
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Biollaz
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D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001562:Benzimidazoles / Q000493:pharmacokinetics / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000493:pharmacokinetics / Q000494:pharmacology; D002986:Clinical Trials as Topic; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics / Q000494:pharmacology; D019808:Losartan; D013777:Tetrazoles / Q000493:pharmacokinetics / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D000068756:Valsartan; D000092502:Renin Inhibitors
D000804:Angiotensin II; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007093:Imidazoles; D019808:Losartan; D013777:Tetrazoles; D014633:Valine; D000068756:Valsartan; D000092502:Renin Inhibitors; C077793:candesartan cilexetil