Document Detail

Integrating drug pharmacokinetics for phenotyping individual renin response to angiotensin II blockade in humans.
MedLine Citation:
PMID:  15023936     Owner:  NLM     Status:  MEDLINE    
Renin release into plasma has been used to investigate the drug dose-dependence of renin-angiotensin system inhibition because it is proportional to the interruption of the permanent negative feedback loop of angiotensin II on renin secretion. We investigated the 24-hour between-subject differences in renin profiles by analyzing the time-dependence of individual renin responses in 16 mildly sodium-depleted normotensive subjects exposed in a 4-period crossover study to single oral doses of 8- and 16-mg (C8 and C16) candesartan cilexetil and 80- and 160-mg (V80 and V160) valsartan. C8 had a similar effect to V160 in terms of the increase in active renin concentration and decrease in blood pressure. C16 had the strongest effect and V80 the weakest effect on renin release. Within- and between-subject variability was more marked for valsartan pharmacokinetics than for candesartan pharmacokinetics and influenced variability in renin response. To eliminate some of the variability caused by the pharmacokinetics of each drug, we corrected the area under time curve of plasma renin levels by that of plasma drug levels to obtain an individual normalized index of renin release or "renin/pharmacokinetic index". In these experimental conditions, this index was found to be a reproducible individual characteristic affecting renin response, in addition to the pharmacokinetics and pharmacological properties of angiotensin II type-1 receptor antagonists. The pharmacokinetic-pharmacodynamic model of renin release described here could be of value for the identification and investigation of renin release abnormalities in patients with hypertension and for the comparison of renin-angiotensin system blockers.
Michel Azizi; Alvine Bissery; Maxime Lamarre-Cliche; Joël Ménard
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2004-03-15
Journal Detail:
Title:  Hypertension     Volume:  43     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2004 Apr 
Date Detail:
Created Date:  2004-03-26     Completed Date:  2004-08-10     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  785-90     Citation Subset:  IM    
Centre d'Investigations Cliniques, Assistance Publique des Hôpitaux de Paris/INSERM, Hôpital Européen Georges Pompidou, 20-40 rue Leblanc, 75908 Paris cedex 15, France.
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MeSH Terms
Administration, Oral
Angiotensin II / antagonists & inhibitors*
Angiotensin II Type 1 Receptor Blockers*
Area Under Curve
Benzimidazoles / administration & dosage,  pharmacokinetics*,  pharmacology
Biphenyl Compounds / administration & dosage,  pharmacokinetics*,  pharmacology
Blood Pressure / drug effects
Cross-Over Studies
Diet, Sodium-Restricted
Diuretics / pharmacology
Dose-Response Relationship, Drug
Double-Blind Method
Furosemide / pharmacology
Genetic Variation
Juxtaglomerular Apparatus / drug effects,  secretion
Renin / blood*,  secretion
Renin-Angiotensin System / drug effects*
Reproducibility of Results
Tetrazoles / administration & dosage,  pharmacokinetics*,  pharmacology
Valine / administration & dosage,  analogs & derivatives,  pharmacokinetics*,  pharmacology
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Benzimidazoles; 0/Biphenyl Compounds; 0/Diuretics; 0/Tetrazoles; 11128-99-7/Angiotensin II; 137862-53-4/valsartan; 54-31-9/Furosemide; 7004-03-7/Valine; EC; R85M2X0D68/candesartan cilexetil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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