Журнал фармаконадзора

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Assessment of Endogenous Biochemical Composites Emphasizing Drug Interaction of Cardiovascular Combined Dosage Formulation in Marketed Product

Rakesh Das and Tapan Kumar Pal

The study reveals the investigational approaches of a Cardiovascular formulated tablet dosage i.e, Atorvastatin (ATVS) & Olmesartan (OLM) after getting negative feedbacks on pharmaceutical market.

A simple, sensitive, precise and rapid analysis under highly sophisticated LCMS/MS system to evaluate the endogenous biochemical composites like Aldosterone (ALD), Angiotensin-II (ANG-II) and Mevalonate (MVA) in plasma concentration level, which associate with mentioned drugs pharmacology. The methods were developed and validated for the same to analyze plasma concentration level among 20 patient volunteers pre-administered with targeted combined tablet dosage.

Chromatographic peaks of standard and internal standard exhibits excellent regression curve line and correlative coefficient, r2 =0.998, 0.999 & 0.999 of ALD, ANG-II & MVA respectively. The quality control profile of accuracy, mean% recovery is range between 90.6-99.13% & 88.2-96.3% respectively of endogenous bio-analytes. And inter-day & intraday precision % RSD (Relative Std. Dev.) is ranges from 1.60-1.90 of the same. Analytical reports represent the lower concentration of ALD after ATVS (Atorvastatin)+OLM (Olmesartan) therapy compare to without drug. But, in case of ANG-II, it is completely inverse and MVA conc. lowers equally in ATVS+OLM and ATVS (individual therapy).

ALD & ANG-II are physiologically responsible for hypertension while MVA for cholesterol biosynthesis. Thus, study concludes that OLM bioavailability approaches get retarded in compare to unchanged bio-availability of ATVS in the combined (ATVS+OLM) formulation and stands weak antihypertensive activity compare to individual therapy, reason might be due to pharmacokinetic interaction. So, its fails the expected synergism.