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A study of the pharmacokinetic interactions of the direct renin inhibitor aliskiren with allopurinol, celecoxib and cimetidine in healthy subjects.
Curr Med Res Opin. 2008 Mar; 24(3):717-26.CM

Abstract

OBJECTIVE

Aliskiren is the first in a new class of orally effective direct renin inhibitors approved for the treatment of hypertension. This multiple-dose study investigated the potential for pharmacokinetic interactions between aliskiren and three drugs, each predominantly eliminated by a different clearance/metabolic pathway: allopurinol (glomerular filtration), celecoxib (cytochrome P450 metabolism) and cimetidine (P-glycoprotein and organic anion/cation transporters).

RESEARCH DESIGN AND METHODS

Three open-label, multiple-dose studies in healthy subjects investigated possible pharmacokinetic interactions between aliskiren 300 mg od and allopurinol 300 mg od (n = 20), celecoxib 200 mg bid (n = 22), or cimetidine 800 mg od (n = 22). Subjects received aliskiren alone or co-administered with allopurinol, celecoxib or cimetidine. Allopurinol and celecoxib were also administered alone and in combination with aliskiren. Plasma drug concentrations were determined by LC/MS/MS.

RESULTS

Co-administration of aliskiren with allopurinol had no effect on allopurinol AUC(tau) (ratio of geometric means 0.93 [90% CI, 0.88, 0.98]) or oxypurinol AUC(tau) (mean ratio 1.12 [90% CI, 1.08, 1.16]) and C(max) (mean ratio 1.08 [90% CI, 1.04, 1.13]), with 90% CI within the bioequivalence range 0.80-1.25, and a minor effect on allopurinol C(max) (mean ratio 0.88 [90% CI, 0.78, 1.00]). Aliskiren co-administration had no effect on AUC(tau) or C(max) of celecoxib (mean ratios and 90% CI within range 0.80-1.25). Neither allopurinol nor celecoxib significantly altered aliskiren AUC(tau) or C(max) (geometric mean ratios 0.88-1.02 with 90% CI including 1.00, but with some 90% CI outside the 0.80-1.25 range due to high variability). Co-administration of aliskiren with cimetidine increased aliskiren AUC(tau) by 20% (mean ratio 1.20 [90% CI, 1.07, 1.34]) and C(max) by 25% (mean ratio 1.25 [90% CI, 0.98, 1.59]).

CONCLUSIONS

In this multiple-dose study, aliskiren showed no clinically relevant pharmacokinetic interactions when co-administered with allopurinol, celecoxib or cimetidine in healthy subjects.

Authors+Show Affiliations

Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. surya.ayalasomayajula@novartis.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18234150

Citation

Ayalasomayajula, Surya, et al. "A Study of the Pharmacokinetic Interactions of the Direct Renin Inhibitor Aliskiren With Allopurinol, Celecoxib and Cimetidine in Healthy Subjects." Current Medical Research and Opinion, vol. 24, no. 3, 2008, pp. 717-26.
Ayalasomayajula S, Tchaloyan S, Yeh CM, et al. A study of the pharmacokinetic interactions of the direct renin inhibitor aliskiren with allopurinol, celecoxib and cimetidine in healthy subjects. Curr Med Res Opin. 2008;24(3):717-26.
Ayalasomayajula, S., Tchaloyan, S., Yeh, C. M., Bizot, M. N., Dieterich, H. A., Howard, D., & Dole, W. P. (2008). A study of the pharmacokinetic interactions of the direct renin inhibitor aliskiren with allopurinol, celecoxib and cimetidine in healthy subjects. Current Medical Research and Opinion, 24(3), 717-26. https://doi.org/10.1185/030079908X260934
Ayalasomayajula S, et al. A Study of the Pharmacokinetic Interactions of the Direct Renin Inhibitor Aliskiren With Allopurinol, Celecoxib and Cimetidine in Healthy Subjects. Curr Med Res Opin. 2008;24(3):717-26. PubMed PMID: 18234150.
* 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 allopurinol, celecoxib and cimetidine in healthy subjects. AU - Ayalasomayajula,Surya, AU - Tchaloyan,Stéphanie, AU - Yeh,Ching-Ming, AU - Bizot,Marie-Noelle, AU - Dieterich,Hans Armin, AU - Howard,Dan, AU - Dole,William P, Y1 - 2008/01/29/ PY - 2008/2/1/pubmed PY - 2008/6/14/medline PY - 2008/2/1/entrez SP - 717 EP - 26 JF - Current medical research and opinion JO - Curr Med Res Opin VL - 24 IS - 3 N2 - OBJECTIVE: Aliskiren is the first in a new class of orally effective direct renin inhibitors approved for the treatment of hypertension. This multiple-dose study investigated the potential for pharmacokinetic interactions between aliskiren and three drugs, each predominantly eliminated by a different clearance/metabolic pathway: allopurinol (glomerular filtration), celecoxib (cytochrome P450 metabolism) and cimetidine (P-glycoprotein and organic anion/cation transporters). RESEARCH DESIGN AND METHODS: Three open-label, multiple-dose studies in healthy subjects investigated possible pharmacokinetic interactions between aliskiren 300 mg od and allopurinol 300 mg od (n = 20), celecoxib 200 mg bid (n = 22), or cimetidine 800 mg od (n = 22). Subjects received aliskiren alone or co-administered with allopurinol, celecoxib or cimetidine. Allopurinol and celecoxib were also administered alone and in combination with aliskiren. Plasma drug concentrations were determined by LC/MS/MS. RESULTS: Co-administration of aliskiren with allopurinol had no effect on allopurinol AUC(tau) (ratio of geometric means 0.93 [90% CI, 0.88, 0.98]) or oxypurinol AUC(tau) (mean ratio 1.12 [90% CI, 1.08, 1.16]) and C(max) (mean ratio 1.08 [90% CI, 1.04, 1.13]), with 90% CI within the bioequivalence range 0.80-1.25, and a minor effect on allopurinol C(max) (mean ratio 0.88 [90% CI, 0.78, 1.00]). Aliskiren co-administration had no effect on AUC(tau) or C(max) of celecoxib (mean ratios and 90% CI within range 0.80-1.25). Neither allopurinol nor celecoxib significantly altered aliskiren AUC(tau) or C(max) (geometric mean ratios 0.88-1.02 with 90% CI including 1.00, but with some 90% CI outside the 0.80-1.25 range due to high variability). Co-administration of aliskiren with cimetidine increased aliskiren AUC(tau) by 20% (mean ratio 1.20 [90% CI, 1.07, 1.34]) and C(max) by 25% (mean ratio 1.25 [90% CI, 0.98, 1.59]). CONCLUSIONS: In this multiple-dose study, aliskiren showed no clinically relevant pharmacokinetic interactions when co-administered with allopurinol, celecoxib or cimetidine in healthy subjects. SN - 1473-4877 UR - https://www.unboundmedicine.com/medline/citation/18234150/A_study_of_the_pharmacokinetic_interactions_of_the_direct_renin_inhibitor_aliskiren_with_allopurinol_celecoxib_and_cimetidine_in_healthy_subjects_ L2 - https://www.tandfonline.com/doi/full/10.1185/030079908X260934 DB - PRIME DP - Unbound Medicine ER -