Individualization of antihypertensive therapy.

Ménard, J; Brunner, Heinrich; Waeber, Bernard; Plouin, P F; Burnier, Michel

doi:10.1161/01.hyp.12.5.526

Cited by 12 publications

(8 citation statements)

References 9 publications

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“…Similar results were obtained with [58,59] , any of which could be substituted for primary osteoblastic stromal cells in co-cultures with spleen cells, to result in the formation of osteoclast-like cells in the presence of 1,25(OH)2D3. These studies highlighted the fact that the ability to promote osteoclast formation was one distributed within the osteoblast lineage, clearly demonstrable in cells early in the lineage, and later shown to be a property also of fibroblasts [60] and of chondrocytes [61] , and even claimed recently for osteocytes [62,63] . On the other hand we did not consider it likely that precursors would be presented to mature, bone-forming osteoblasts in a way that would favour these members of the osteoblast lineage having a role in osteoclast generation.…”

Section: Control Of Osteoclast Formationmentioning

confidence: 99%

Historically significant events in the discovery of RANK/RANKL/OPG

Martın¹

2013

WJO

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After it was suggested 30 years ago that the osteoblast lineage controlled the formation of osteoclasts, methods were developed that established this to be the case, but the molecular controls were elusive. Over more than a decade much evidence was obtained for signaling mechanisms that regulated the production of a membrane -bound regulator of osteoclastogenesis, in the course of which intercellular communication in bone was revealed in its complexity. The discovery of regulation by tumor necrosis factor ligand and receptor families was made in the last few years of the twentieth century, leading since then to a new physiology of bone, and to exciting drug development. Key words: Receptor activator of nuclear factor κB ligand; Osteoprotegerin; Receptor activator of nuclear factor κB; Osteoclasts; Bone biology Core tip: The history of discovery of receptor activator of nuclear factor κB ligand began with the hypothesis that the osteoblast lineage controls osteoclast formation. The hypothesis was confirmed by experiments showing first, that osteoblastic cells were necessary for osteoclast activation, then some years later that osteoblasts were necessary for osteoclast formation in a contact-dependent process. Ultimate confirmation came from mouse genetics, discovering inhibition of osteoblast formation by a secreted tumor necrosis factor (TNF) ligand, followed by discovery of promotion of osteoclast formation by a membrane-bound member of the TNF ligand family that signalled through its receptor in hemopoietic cells to promote osteoclast formation.Martin TJ. Historically significant events in the discovery of RANK/RANKL/OPG. World

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Section: Control Of Osteoclast Formationmentioning

confidence: 99%

Historically significant events in the discovery of RANK/RANKL/OPG

Martın¹

2013

WJO

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Section: T He Angiotensin Converting Enzyme (Ace)mentioning

confidence: 99%

“…3 Qinical studies have shown large interindividual differences in the effect of an ACE inhibitor on blood pressure and the renin-angiotensin system, particularly after the first dose, but little attempt has been made to quantify and optimize the response in individual subjects. 4 There is some evidence that reduction of blood pressure and inhibition of plasma ACE activity are dose-dependent, 5 " 7 but no consistent concentrationeffect relation has been established between plasma drug (or active metabolite) concentration and blood pressure reduction or ACE inhibition. Received May 1, 1989; accepted in revised form October 30, 1989. this is likely to reflect the wide range of intersubject variability in pharmacokinetic responses, particularly when group data are evaluated, there is preliminary evidence that concentration-effect relations for ACE inhibitors can be more readily identified when individual subjects are considered.…”

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confidence: 99%

Kinetic-dynamic relations and individual responses to enalapril.

et al. 1990

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Pharmacoklnetic and phannacodynamic variability largely account for interindividual differences in the response to antihypertensive drugs including angiotensin converting enzyme inhibitors. The factors determining the response to enalapril have been investigated in a placebo-controlled study in essential hypertension. The effects of placebo, the initial dose of enalapril, and long-term (1 and 6 weeks) treatment with enalapril were studied in 13 subjects. By using an integrated kinetic-dynamic model that incorporates a parameter for saturable protein binding, individual responses for blood pressure reduction and angiotensin converting enzyme inhibition were characterized in terms of the maximum effect (E^J and the drug concentration required to produce 50% of E M (0,50). In individual subjects, plasma enalaprilat concentrations could be correlated with falls in blood pressure and changes in plasma angiotensin converting enzyme activity. For the group, E^, was -46.1 ±16.5 and -19.7 ±3.8 mm Hg for systolic and dlastolic blood pressure, respectively, and the corresponding C,50 values were 66.1 ±20.2 and 61.6 ±22.5 ng/ml. For angiotensin converting enzyme inhibition, £ " , (%) and C.50 (ng/ml) were, respectively, 102.4±5 and 19.8±13 after the first dose, 103±5 and 33.4±20J after 1 week, and 101 J±2.2 and 31 J±18.9 after 6 weeks. There was no relation between the responsiveness to enalapril ( E^ or C.50) and patient age or plasma renin activity, but there was a significant positive correlation between E^ and the pretreatment blood pressure. In individual subjects, E^ (first dose) was directly correlated with E mM1 after 1 and 6 weeks. This study, which incorporated kinetic as well as dynamic information to characterize the antihypertensive response to enalapril, has identified enalaprilat concentration-effect relations in individual hypertensive subjects. 3 Qinical studies have shown large interindividual differences in the effect of an ACE inhibitor on blood pressure and the renin-angiotensin system, particularly after the first dose, but little attempt has been made to quantify and optimize the response in individual subjects. 4 There is some evidence that reduction of blood pressure and inhibition of plasma ACE activity are dose-dependent, 5 " 7 but no consistent concentrationeffect relation has been established between plasma drug (or active metabolite) concentration and blood pressure reduction or ACE inhibition. Received May 1, 1989; accepted in revised form October 30, 1989. this is likely to reflect the wide range of intersubject variability in pharmacokinetic responses, particularly when group data are evaluated, there is preliminary evidence that concentration-effect relations for ACE inhibitors can be more readily identified when individual subjects are considered. -13This study uses integrated pharmacokineticpharmacodynamic modeling 14 to investigate and characterize the antihypertensive responses and concentration-effect relations during acute and chronic treatment with enalapril in patients with esse...

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“…[1][2][3][4] Interest has been focused on the identification of demographic, physiological or genetic factors which influence antihypertensive response. [5][6][7] Pre-treatment plasma renin activity (PRA) has been proposed as one of the most promising predictors which could help guide the selection of antihypertensive therapy.…”

Section: Introductionmentioning

confidence: 99%

Comparative Pharmacodynamics of Olmesartan and Azelnidipine in Patients with Hypertension: a Population Pharmacokinetic/Pharmacodynamic Analysis

Yoshihara

Kuramoto

Arakawa

2009

Drug Metabolism and Pharmacokinetics

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The objectives of this study were to identify the factors influencing antihypertensive response to the angiotensin receptor blocker, olmesartan medoxomil, or the calcium channel blocker, azelnidipine, and to discuss the possibility of utilizing them as predictors for drug selection prior to therapy. A two-way crossover study of olmesartan medoxomil and azelnidipine was conducted in 29 patients with mild to moderate essential hypertension. The 24-hour ambulatory blood pressure measurements (ABPM) and plasma drug concentrations were obtained on the first and at the end of each treatment period, and were analyzed using population pharmacokinetic/pharmacodynamic (PK/PD) modeling approach. The population PK/PD models considering circadian variations in baseline blood pressure well described the observed plasma drug concentrations and 24-hour ABPM profiles. Pre-treatment plasma renin activity (PRA) was identified as a significant covariate on the maximum drug effect (E(max)) of olmesartan, whereas azelnidpine E(max) was independent of patient background characteristics investigated. No patient was found to have a high E(max) to one agent who also had a high E(max) to the other. In conclusion, the effects of olmesartan medoxomil and azelnidipine were modestly correlated with pharmacokinetic profiles, and the pre-treatment PRA level could be a useful determinant of responsiveness in selecting olmesartan medoxomil and azelnidipine.

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Individualization of antihypertensive therapy.

Cited by 12 publications

References 9 publications

Historically significant events in the discovery of RANK/RANKL/OPG

Historically significant events in the discovery of RANK/RANKL/OPG

Kinetic-dynamic relations and individual responses to enalapril.

Comparative Pharmacodynamics of Olmesartan and Azelnidipine in Patients with Hypertension: a Population Pharmacokinetic/Pharmacodynamic Analysis

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