Pharmacokinetics and pharmacodynamics of aliskiren/hydrochlorothiazide
single-pill combination tablets and free combination of aliskiren and
hydrochlorothiazide.
Author(s): Yan JH, Jarugula V, Sabo R, Papst CC, Zhang J, Dole WP.
Affiliation(s): Novartis Institutes for BioMedical Research, Inc, Cambridge, MA 02139, USA.
Publication date & source: 2012, J Clin Pharmacol. , 52(5):645-55
Single-pill combinations (SPCs) of complementary antihypertensive agents provide
patients with a simple and effective treatment regimen. To ensure that the
efficacy and safety of an SPC is the same as that for the individual drugs
administered together (free combination), SPC and free-combination formulations
must be shown to be bioequivalent. Three open-label, randomized studies compared
the pharmacokinetics of SPC tablets of the direct renin inhibitor aliskiren and
hydrochlorothiazide (HCT), at doses of 150/25, 300/12.5, and 300/25 mg, with the
corresponding free combinations in healthy volunteers. Data from 2 randomized,
double-blinded studies of patients with hypertension were used to assess
inhibition of plasma renin activity (PRA) by the aliskiren/HCT 300/25 mg SPC and
the free combination. At all dose combinations, aliskiren and HCT systemic drug
exposure was similar when administered as an SPC or free combination, indicating
bioequivalence. Aliskiren/HCT 300/25 mg SPC inhibited PRA to the same extent as
the free combination. HCT alone increased PRA through activation of the
renin-angiotensin system; aliskiren prevented this diuretic-induced increase to
the same extent when administered as the free combination or as the SPC. In
conclusion, aliskiren/HCT SPCs are pharmacokinetically and pharmacodynamically
bioequivalent to aliskiren and HCT in free combination.
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