American Journal of Cardiovascular Drugs

, Volume 10, Issue 2, pp 95–103

Preservation of Bioavailability of Ingredients and Lack of Drug-Drug Interactions in a Novel Five-Ingredient Polypill (Polycap™)

A Five-Arm Phase I Crossover Trial in Healthy Volunteers
  • Anil Patel
  • Tarang Shah
  • Gaurang Shah
  • Vijay Jha
  • Chinmoy Ghosh
  • Jagruti Desai
  • Bakulesh Khamar
  • Bhaswat S. Chakraborty
Original Research Article

DOI: 10.2165/11532170-000000000-00000

Cite this article as:
Patel, A., Shah, T., Shah, G. et al. Am J Cardiovasc Drugs (2010) 10: 95. doi:10.2165/11532170-000000000-00000

Abstract

Background

The Polycap™ (polypill; aspirin [acetylsalicylic acid], ramipril, simvastatin, atenolol, and hydrochlorothiazide) was found to be safe and effective for reducing multiple cardiovascular risk factors in The Indian Polycap™ Study (TIPS).

Objective

We evaluated the bioavailability of each ingredient of the Polycap™ and determined any drug-drug interactions relative to single component reference preparations.

Methods

The bioavailability of the ingredients of the Polycap™ (T; test) when formulated as a single capsule was compared with that of identical capsules with each of its ingredients administered separately (R; reference) in a five-arm, randomized, single-dose, two-period, two-treatment, two-sequence, crossover trial with at least a 2-week washout period in a total of 195 healthy volunteers. Plasma concentrations of each drug and, where applicable, its active metabolite were measured using validated liquid chromatographytandem mass spectrometry and ultra-performance liquid chromatography. Mean pharmacokinetic parameters and their standard deviations were computed for each analyte.

Results

Comparative bioavailability was computed and no drug-drug interactions and no difference in comparative bioavailability were concluded for each ingredient based on point estimates of the T/R ratio of the geometric means falling within 80–125% for peak plasma concentration (Cmax), area under the plasma concentration-time curve from time zero to the last measurable concentration (AUCt), and AUC from time zero to infinity (AUC). The T/R ratio for Cmax, AUCt and AUC∞ was within 80–125% for atenolol, hydrochlorothiazide, ramipril, ramiprilat and dose-normalized salicylic acid. However, for simvastatin, the T/R point estimates for Cmax, AUCt and AUC∞ for Ln-transformed data were significantly lower (∼3–4%) than the lower bound of 80%. For its active metabolite, simvastatin acid, these estimates were significantly higher (∼25–35%) than the higher bound of 125%. Thus, the increased bioavailability of active simvastatin acid appeared to compensate for the loss of bioavailability of simvastatin.

Conclusion

The Polycap™ was found to be effective and safe in the previously published TIPS trial. The present study in healthy volunteers establishes that Polycap™ is safe (no serious adverse events) and well tolerated, and that there is no indication of pharmacokinetic drug-drug interactions for any of the ingredients, with their bioavailabilities being well preserved.

Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  • Anil Patel
    • 1
  • Tarang Shah
    • 1
  • Gaurang Shah
    • 1
  • Vijay Jha
    • 1
  • Chinmoy Ghosh
    • 1
  • Jagruti Desai
    • 1
  • Bakulesh Khamar
    • 1
  • Bhaswat S. Chakraborty
    • 1
  1. 1.Contract Research OrganizationCadila Pharmaceuticals LtdAhmedabadIndia