Lovastatin/Nicotinic Acid

An extended-release (ER) niacin and lovastatin fixed-dose combination has been developed for the treatment of primary hypercholesterolemia and mixed dyslipidemia. The purpose of the present study was to examine the drug interaction between niacin and lovastatin after multi-dose oral administration of lovastatin/niacin ER combination in healthy Chinese volunteers. A single-center, randomized, open-label, 5-period crossover study was conducted in thirty healthy volunteers aged 18 to 45 years with a washout period of 8 days. Subjects were randomized to receive multiple doses of treatment A (1 500 mg niacin ER tablet), B (1 20 mg lovastatin tablet), C (1 20 mg lovastatin and 500 mg niacin-ER tablet), D (2 10 mg lovastatin and 350 mg niacin-ER tablets) or E (2 10 mg lovastatin and 500 mg niacin-ER tablets) in 1 of 5 sequences (ABCDE, BCDEA, CDEAB, DEABC, EABCD) per period. Lovastatin, niacin and its metabolites (nicotinuric acid and nicotinamide) were determined in plasma by LC/MS method. Pharmacokinetic parameters were calculated, and least square mean ratios and 90% confidence intervals for Cmax⁡ and AUC (0–24) were determined for lovastatin/niacin ER versus niacin ER or lovastatin. It revealed that the formulation had no potential drug interaction in healthy Chinese volunteers when the dosage was increased from 500 mg to 1000 mg.

Most cardiovascular diseases need to be treated by more than a simple drug and the use of combination products diminishes noncompliance. Advicor(®) as a combination product of a vitamin and a fat lowering agent has no monograph in official pharmacopeias for its quality control purposes. In this study, first and third derivative signals for NA and LV quantitation at the two pairs of wavelengths, 261 and 273 nm; 245 and 249 nm were monitored with the addition of standard solutions of NA or LV, respectively. The limits of detection were 0.03 and 0.32 mg/L for LV and NA, respectively. The limits of quantitation were 0.09 and 0.78 mg/L for LV and NA, respectively. RSD% for both interday and intraday precision was lower than 2.6 and 2.7% for LV and NA, respectively. Selectivity of the method was assessed for both degradation products produced in stress conditions and common excipients that may present in the pharmaceutical dosage forms. The recommended procedure was successfully applied to real samples.