In Vivo Safety Assessment of the Plant Growth Promoting Rhizobacterium Bacillus cereus RS87 and Rhizo-product.

Aims: To assess the acute toxicity and skin irritation potential of a rhizobacterium Bacillus cereus RS87 and the rhizo-product in rats and rabbits. Study Design: Adult Wistar rats were gavaged with a single dose of B. cereus RS87 in acute oral toxicity test and were applied with single doses of rhizo-product for 24 hours in acute dermal toxicity test. New Zealand albino rabbits were applied with 0.5g rhizoproduct in acute dermal irritation test. Place and Duration of Study: Pharmaceutical and Natural Products Department, Thailand Institute of Scientific and Technological Research (TISTR), Pathum Thani, Thailand, between November 2013 and March 2014. Methodology: Animal toxicity studies were carried out by the methods described in the Organization for Economic Co-operation and Development (OECD) test guidelines. Mortality data of animals were used to determine the median lethal dose (LD50) values after oral and dermal exposures to B. cereus RS87 and the rhizo-product along with distilled water as control. The skin irritation potential of the rhizo-product was evaluated in rabbits. Distilled water was used as a control. The average weight gains were calculated and gross examination at necropsy was performed. Results: No mortality and no signs of toxicity were observed. The oral LD50 of B. cereus RS87 and dermal LD50 of rhizo-product in rats were greater than 9x108 CFU kg-1 and 15,000 mg kg-1(about 4.5x108 CFU kg-1), respectively. However, significant decrease in mean weight gain in the high-dose groups when compared to controls (21.40+/-1.47 versus 28.40 +/- 0.24 (male); 13.80+/-2.57 versus 20.20+/-0.58 (female)) were reported at day 8 after 24-hour dermal exposure to rhizo-product. No pathological changes in major organs were observed at necropsy. Conclusion: B. cereus RS87 and the rhizo-product (about 3x107 CFU/g) have low acute toxicity and very low skin irritation potential, which was considered safe for humans. However, adverse effect needed to be further explored in the field experiment or in practical use.

Relative bioavailability study of 20-mg enalapril tablets in healthy male volunteers.

The pharmacokinetic and relative bioavailability studies of 20-mg enalapril tablets, the test product manufactured by Biolab, Thailand compared to the reference product (Merck Sharp & Dohme, USA) was conducted in 14 healthy Thai male volunteers following a single dose, two-period, crossover design. Each subject received 20-mg enalapril tablets of both formulations with a 1-week washout period. Plasma samples collected over a 24-h period after administration were analyzed by LC/MS/MS. Pharmacokinetic parameters were determined by using non-compartmental analysis. Regarding bioequivalence testing, the 90 per cent confidence intervals of Cmax and AUC(0-infinity) ratios (test/reference) of enalapril were 101.8-134.9 per cent and 105.9-121.4 per cent and those of enalaprilat were 104.2-122.3 per cent and 104.5-118.1 per cent. Based on the European bioequivalence guideline, the 90 per cent confidence intervals of Cmax and AUC(0-infinity) ratios of both parent and metabolite forms were within the acceptable ranges of 70-143 per cent and 80-125 per cent, respectively. It was concluded that the test formulation was bioequivalent to the reference formulation and both formulations can be used interchangeably in clinical practice.

Bioequivalence study of ondansetron tablet in healthy Thai male volunteers.

OBJECTIVES: To assess the average bioequivalence of two formulations of 8-mg ondansetron tablets--test product (Unison Laboratories, Thailand) and reference product (Glaxo Wellcome, USA)--in 14 healthy Thai male volunteers. MATERIAL AND METHOD: In a randomized, single dose, fasting, two-period, crossover study design with a 1-week washout period, each subject received an 8-mg ondansetron tablet. Serum samples were collected over a 24-hour period after administration. Subsequently serum concentrations of ondansetron were analyzed by using a validated HPLC-UV method. Pharmacokinetic parameters were determined by using non-compartmental analysis. RESULTS: No significant difference was observed in any of the pharmacokinetic parameters analyzed. The time to reach the maximal concentration (Tmax, hour), the peak concentration (Cmax, ng/ ml) and the area under the concentration-time curve (AUC(0-infinity), ng x h/ml) of ondansetron for reference and test preparations were 2.6 + 1.8 vs 2.2 + 0.6, 49.5 +/- 18.9 vs 48.5 +/- 13.7 and 352.2 +/- 184.7 vs 323.8 +/- 154.5, respectively. The 90 per cent confidence intervals for Test/Reference ratio of Cmax and AUC(0-infinity) were found within the bioequivalence range of 80-125 per cent (90.3-110.0% and 88.4-99.6%, respectively). CONCLUSION: The bioequivalence of these two ondansetron preparations was demonstrated.

Bioequivalence study of enalapril tablets in healthy Thai male volunteers.

The bioequivalence study of 5-mg enalapril tablets, Enaril (Biolab, Thailand) compared to Renitec (Merck Sharp & Dohme, USA) was conducted in 14 healthy Thai male volunteers following a single dose, two-period, crossover design. Each subject received 4 tablets of 5-mg enalapril tablets of both formulations with a 1-week washout period. Plasma samples collected over a 24-hour period after administration were analyzed by LC/MS/MS. Pharmacokinetic parameters were determined by using non-compartmental analysis. Regarding bioequivalence testing, the 90 per cent confidence intervals of Cmax and AUC(0-infinity) ratios (Enaril/Renitec) of enalapril were 86.3-126.1 per cent and 93.0-118.5 per cent and those of enalaprilat were 86.4-124.1 per cent and 90.3-116.8 per cent. Based on the European bioequivalence guideline, the 90 per cent confidence interval of Cmax and AUC(0-infinity) ratios of both parent and metabolite forms were within acceptable ranges of 70-143 per cent and 80-125 per cent, respectively. It was concluded that Enaril 5 mg tablet was bioequivalent to Renitec 5 mg tablet.