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Influence of Body Weight and Gender on the Pharmacokinetics, Pharmacodynamics, and Antihypertensive Efficacy of Aliskiren
Author(s) -
Jarugula Venkateswar,
Yeh ChingMing,
Howard Dan,
Bush Christopher,
Keefe Deborah L.,
Dole William P.
Publication year - 2010
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009359525
Subject(s) - aliskiren , pharmacokinetics , pharmacodynamics , medicine , plasma renin activity , renin inhibitor , body mass index , endocrinology , blood pressure , area under the curve , pharmacology , renin–angiotensin system
Gender and body weight influence the pharmacokinetics and pharmacodynamics of many drugs. This pooled analysis of 17 clinical studies evaluated the effect of gender, body mass index (BMI), body weight, and lean body weight (LBW) on the pharmacokinetics of the direct renin inhibitor aliskiren in healthy volunteers (n = 392). A separate pooled analysis of 5 clinical studies in patients with hypertension (n = 2327) assessed the influence of gender and BMI on the effects of aliskiren on plasma renin activity and blood pressure. Area under the aliskiren plasma concentration‐time curve (AUC τ ) was 22% lower and the peak aliskiren plasma concentration (C max ) was 24% lower in men than women (P < .05). BMI was not significantly correlated with AUC τ (r = 0.005; P = .917); AUC τ was negatively correlated with body weight (r = −0.235; P < .0001) and LBW (r = −0.295; P < .0001). Results were similar for C max . Adjusting individual aliskiren AUC τ and C max values for overall mean body weight or LBW abolished gender differences. Based on r 2 values, LBW variation accounted for 8.9% of aliskiren AUC τ variation. In patients with hypertension, gender and BMI did not significantly influence the effects of aliskiren on plasma renin activity or blood pressure. It was concluded that lower systemic exposure to aliskiren in men versus women relates to differences in body weight; neither gender nor body weight has clinically relevant effects on the pharmacokinetics or pharmacodynamics of aliskiren.