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Lack of pharmacokinetic interactions of aliskiren, a novel direct renin inhibitor for the treatment of hypertension, with the antihypertensives amlodipine, valsartan, hydrochlorothiazide (HCTZ) and ramipril in healthy volunteers.
Int J Clin Pract. 2006 Nov; 60(11):1343-56.IJ

Abstract

Aliskiren is a novel, orally active direct renin inhibitor that lowers blood pressure alone and in combination with existing antihypertensive agents. As aliskiren does not affect cytochrome P450 enzyme activities, is minimally metabolised, and is not extensively protein bound, the potential for drug interactions is predicted to be low. Four open-label studies investigated the pharmacokinetic interactions between aliskiren 300 mg and the antihypertensive drugs amlodipine 10 mg (n = 18), valsartan 320 mg (n = 18), hydrochlorothiazide 25 mg (HCTZ, n = 22) and ramipril 10 mg (n = 17) in healthy subjects. In each study, subjects received multiple once-daily doses of aliskiren and the test antihypertensive drug alone or in combination in two dosing periods separated by a drug-free washout period. Plasma concentrations of drugs were determined by liquid chromatography and mass spectrometry methods. At steady state, relatively small changes in exposure to aliskiren were observed when aliskiren was co-administered with amlodipine (AUC(tau) increased by 29%, p = 0.032), ramipril (C(max,ss) increased by 31%, p = 0.043), valsartan (AUC(tau) decreased by 26%, p = 0.002) and HCTZ (C(max,ss) decreased by 22%, p = 0.039). Co-administration with aliskiren resulted in small changes in exposure to ramipril (AUC(tau) increased by 22%, p = 0.002), valsartan (AUC(tau) decreased by 14%, p = 0.062) and HCTZ (AUC(tau) decreased by 10% and C(max,ss) by 26%, both p < 0.001). All other changes in pharmacokinetic parameters were also small, and not statistically significant. None of the observed pharmacokinetic changes was considered clinically relevant. Aliskiren inhibited plasma renin activity (PRA) and also prevented the reactive rise in PRA induced by valsartan. The most commonly reported adverse events were headache, dizziness and gastrointestinal symptoms (all mild in severity), which were similar in frequency during antihypertensive drug treatment alone and in combination with aliskiren except for an increase in dizziness during treatment with the combination of aliskiren and HCTZ. In conclusion, aliskiren shows no clinically relevant pharmacokinetic interactions and is generally well tolerated when administered in combination with amlodipine, valsartan, HCTZ or ramipril.

Authors+Show Affiliations

Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17073832

Citation

Vaidyanathan, S, et al. "Lack of Pharmacokinetic Interactions of Aliskiren, a Novel Direct Renin Inhibitor for the Treatment of Hypertension, With the Antihypertensives Amlodipine, Valsartan, Hydrochlorothiazide (HCTZ) and Ramipril in Healthy Volunteers." International Journal of Clinical Practice, vol. 60, no. 11, 2006, pp. 1343-56.
Vaidyanathan S, Valencia J, Kemp C, et al. Lack of pharmacokinetic interactions of aliskiren, a novel direct renin inhibitor for the treatment of hypertension, with the antihypertensives amlodipine, valsartan, hydrochlorothiazide (HCTZ) and ramipril in healthy volunteers. Int J Clin Pract. 2006;60(11):1343-56.
Vaidyanathan, S., Valencia, J., Kemp, C., Zhao, C., Yeh, C. M., Bizot, M. N., Denouel, J., Dieterich, H. A., & Dole, W. P. (2006). Lack of pharmacokinetic interactions of aliskiren, a novel direct renin inhibitor for the treatment of hypertension, with the antihypertensives amlodipine, valsartan, hydrochlorothiazide (HCTZ) and ramipril in healthy volunteers. International Journal of Clinical Practice, 60(11), 1343-56.
Vaidyanathan S, et al. Lack of Pharmacokinetic Interactions of Aliskiren, a Novel Direct Renin Inhibitor for the Treatment of Hypertension, With the Antihypertensives Amlodipine, Valsartan, Hydrochlorothiazide (HCTZ) and Ramipril in Healthy Volunteers. Int J Clin Pract. 2006;60(11):1343-56. PubMed PMID: 17073832.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lack of pharmacokinetic interactions of aliskiren, a novel direct renin inhibitor for the treatment of hypertension, with the antihypertensives amlodipine, valsartan, hydrochlorothiazide (HCTZ) and ramipril in healthy volunteers. AU - Vaidyanathan,S, AU - Valencia,J, AU - Kemp,C, AU - Zhao,C, AU - Yeh,C-M, AU - Bizot,M-N, AU - Denouel,J, AU - Dieterich,H A, AU - Dole,W P, PY - 2006/11/1/pubmed PY - 2007/2/28/medline PY - 2006/11/1/entrez SP - 1343 EP - 56 JF - International journal of clinical practice JO - Int J Clin Pract VL - 60 IS - 11 N2 - Aliskiren is a novel, orally active direct renin inhibitor that lowers blood pressure alone and in combination with existing antihypertensive agents. As aliskiren does not affect cytochrome P450 enzyme activities, is minimally metabolised, and is not extensively protein bound, the potential for drug interactions is predicted to be low. Four open-label studies investigated the pharmacokinetic interactions between aliskiren 300 mg and the antihypertensive drugs amlodipine 10 mg (n = 18), valsartan 320 mg (n = 18), hydrochlorothiazide 25 mg (HCTZ, n = 22) and ramipril 10 mg (n = 17) in healthy subjects. In each study, subjects received multiple once-daily doses of aliskiren and the test antihypertensive drug alone or in combination in two dosing periods separated by a drug-free washout period. Plasma concentrations of drugs were determined by liquid chromatography and mass spectrometry methods. At steady state, relatively small changes in exposure to aliskiren were observed when aliskiren was co-administered with amlodipine (AUC(tau) increased by 29%, p = 0.032), ramipril (C(max,ss) increased by 31%, p = 0.043), valsartan (AUC(tau) decreased by 26%, p = 0.002) and HCTZ (C(max,ss) decreased by 22%, p = 0.039). Co-administration with aliskiren resulted in small changes in exposure to ramipril (AUC(tau) increased by 22%, p = 0.002), valsartan (AUC(tau) decreased by 14%, p = 0.062) and HCTZ (AUC(tau) decreased by 10% and C(max,ss) by 26%, both p < 0.001). All other changes in pharmacokinetic parameters were also small, and not statistically significant. None of the observed pharmacokinetic changes was considered clinically relevant. Aliskiren inhibited plasma renin activity (PRA) and also prevented the reactive rise in PRA induced by valsartan. The most commonly reported adverse events were headache, dizziness and gastrointestinal symptoms (all mild in severity), which were similar in frequency during antihypertensive drug treatment alone and in combination with aliskiren except for an increase in dizziness during treatment with the combination of aliskiren and HCTZ. In conclusion, aliskiren shows no clinically relevant pharmacokinetic interactions and is generally well tolerated when administered in combination with amlodipine, valsartan, HCTZ or ramipril. SN - 1368-5031 UR - https://www.unboundmedicine.com/medline/citation/17073832/Lack_of_pharmacokinetic_interactions_of_aliskiren_a_novel_direct_renin_inhibitor_for_the_treatment_of_hypertension_with_the_antihypertensives_amlodipine_valsartan_hydrochlorothiazide__HCTZ__and_ramipril_in_healthy_volunteers_ L2 - https://doi.org/10.1111/j.1742-1241.2006.01164.x DB - PRIME DP - Unbound Medicine ER -