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A study of the pharmacokinetic interactions of the direct renin inhibitor aliskiren with metformin, pioglitazone and fenofibrate in healthy subjects.
Curr Med Res Opin. 2008 Aug; 24(8):2313-26.CM

Abstract

OBJECTIVE

Hypertension and type 2 diabetes are common comorbidities, thus many patients receiving antihypertensive medication require concomitant therapy with hypoglycemic or lipid-lowering drugs. The aim of these three studies was to investigate the pharmacokinetics, safety and tolerability of aliskiren, a direct renin inhibitor for the treatment of hypertension, co-administered with the glucose-lowering agents metformin or pioglitazone or the lipid-lowering agent fenofibrate in healthy volunteers.

METHODS

In three open-label, multiple-dose studies, healthy volunteers (ages 18 to 45 years) received once-daily treatment with either metformin 1000 mg (n = 22), pioglitazone 45 mg (n = 30) or fenofibrate 200 mg (n = 21) and aliskiren 300 mg, administered alone or co-administered in a two-period study design. Blood samples were taken frequently on the last day of each treatment period to determine plasma drug concentrations.

RESULTS

Co-administration of aliskiren with metformin decreased aliskiren area under the plasma concentration- time curve during the dose interval (AUC(tau)) by 27% (geometric mean ratio [GMR] 0.73; 90% confidence interval [CI] 0.64, 0.84) and maximum observed plasma concentration (C(max)) by 29% (GMR 0.71; 90% CI 0.56, 0.89) but these changes were not considered clinically relevant. Co-administration of aliskiren with fenofibrate had no effect on aliskiren AUC (GMR 1.05; 90% CI 0.96, 1.16) or C(max) (GMR 1.05; 90% CI 0.80, 1.38); similarly, co-administration of aliskiren with pioglitazone had no effect on aliskiren AUC(tau) (GMR 1.05; 90% CI 0.98, 1.13) or C(max) (GMR 1.01; 90% CI 0.84, 1.20). All other AUC and C(max) GMRs for aliskiren, metformin, pioglitazone, ketopioglitazone, hydroxypioglita-zone and fenofibrate were close to unity and the 90% CI were contained within the bioequivalence range of 0.80 to 1.25.

CONCLUSION

Co-administration of aliskiren with metformin, pioglitazone or fenofibrate had no significant effect on the pharmacokinetics of these drugs in healthy volunteers. These findings indicate that aliskiren can be co-administered with metformin, pioglitazone or fenofibrate without the need for dose adjustment.

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 available

Pub Type(s)

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

Language

eng

PubMed ID

18786303

Citation

Vaidyanathan, Sujata, et al. "A Study of the Pharmacokinetic Interactions of the Direct Renin Inhibitor Aliskiren With Metformin, Pioglitazone and Fenofibrate in Healthy Subjects." Current Medical Research and Opinion, vol. 24, no. 8, 2008, pp. 2313-26.
Vaidyanathan S, Maboudian M, Warren V, et al. A study of the pharmacokinetic interactions of the direct renin inhibitor aliskiren with metformin, pioglitazone and fenofibrate in healthy subjects. Curr Med Res Opin. 2008;24(8):2313-26.
Vaidyanathan, S., Maboudian, M., Warren, V., Yeh, C. M., Dieterich, H. A., Howard, D., & Dole, W. P. (2008). A study of the pharmacokinetic interactions of the direct renin inhibitor aliskiren with metformin, pioglitazone and fenofibrate in healthy subjects. Current Medical Research and Opinion, 24(8), 2313-26. https://doi.org/10.1185/03007990802259354
Vaidyanathan S, et al. A Study of the Pharmacokinetic Interactions of the Direct Renin Inhibitor Aliskiren With Metformin, Pioglitazone and Fenofibrate in Healthy Subjects. Curr Med Res Opin. 2008;24(8):2313-26. PubMed PMID: 18786303.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A study of the pharmacokinetic interactions of the direct renin inhibitor aliskiren with metformin, pioglitazone and fenofibrate in healthy subjects. AU - Vaidyanathan,Sujata, AU - Maboudian,Mojdeh, AU - Warren,Vance, AU - Yeh,Ching-Ming, AU - Dieterich,Hans Armin, AU - Howard,Dan, AU - Dole,William P, PY - 2008/9/13/pubmed PY - 2008/12/30/medline PY - 2008/9/13/entrez SP - 2313 EP - 26 JF - Current medical research and opinion JO - Curr Med Res Opin VL - 24 IS - 8 N2 - OBJECTIVE: Hypertension and type 2 diabetes are common comorbidities, thus many patients receiving antihypertensive medication require concomitant therapy with hypoglycemic or lipid-lowering drugs. The aim of these three studies was to investigate the pharmacokinetics, safety and tolerability of aliskiren, a direct renin inhibitor for the treatment of hypertension, co-administered with the glucose-lowering agents metformin or pioglitazone or the lipid-lowering agent fenofibrate in healthy volunteers. METHODS: In three open-label, multiple-dose studies, healthy volunteers (ages 18 to 45 years) received once-daily treatment with either metformin 1000 mg (n = 22), pioglitazone 45 mg (n = 30) or fenofibrate 200 mg (n = 21) and aliskiren 300 mg, administered alone or co-administered in a two-period study design. Blood samples were taken frequently on the last day of each treatment period to determine plasma drug concentrations. RESULTS: Co-administration of aliskiren with metformin decreased aliskiren area under the plasma concentration- time curve during the dose interval (AUC(tau)) by 27% (geometric mean ratio [GMR] 0.73; 90% confidence interval [CI] 0.64, 0.84) and maximum observed plasma concentration (C(max)) by 29% (GMR 0.71; 90% CI 0.56, 0.89) but these changes were not considered clinically relevant. Co-administration of aliskiren with fenofibrate had no effect on aliskiren AUC (GMR 1.05; 90% CI 0.96, 1.16) or C(max) (GMR 1.05; 90% CI 0.80, 1.38); similarly, co-administration of aliskiren with pioglitazone had no effect on aliskiren AUC(tau) (GMR 1.05; 90% CI 0.98, 1.13) or C(max) (GMR 1.01; 90% CI 0.84, 1.20). All other AUC and C(max) GMRs for aliskiren, metformin, pioglitazone, ketopioglitazone, hydroxypioglita-zone and fenofibrate were close to unity and the 90% CI were contained within the bioequivalence range of 0.80 to 1.25. CONCLUSION: Co-administration of aliskiren with metformin, pioglitazone or fenofibrate had no significant effect on the pharmacokinetics of these drugs in healthy volunteers. These findings indicate that aliskiren can be co-administered with metformin, pioglitazone or fenofibrate without the need for dose adjustment. SN - 1473-4877 UR - https://www.unboundmedicine.com/medline/citation/18786303/A_study_of_the_pharmacokinetic_interactions_of_the_direct_renin_inhibitor_aliskiren_with_metformin_pioglitazone_and_fenofibrate_in_healthy_subjects_ L2 - http://www.tandfonline.com/doi/full/10.1185/03007990802259354 DB - PRIME DP - Unbound Medicine ER -