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 chromatography-tandem 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 (C(max)), area under the 
plasma concentration-time curve from time zero to the last measurable 
concentration (AUC(t)), and AUC from time zero to infinity (AUC(infinity)). The 
T/R ratio for C(max), AUC(t) and AUC(infinity) was within 80-125% for atenolol, 
hydrochlorothiazide, ramipril, ramiprilat and dose-normalized salicylic acid. 
However, for simvastatin, the T/R point estimates for C(max), AUC(t) and 
AUC(infinity) for Ln-transformed data were significantly lower ( approximately 
3-4%) than the lower bound of 80%. For its active metabolite, simvastatin acid, 
these estimates were significantly higher ( approximately 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.