The Protective Effect of Lercanidipine on Indomethacin-Induced Gastric Ulcers in Rats

Abstract Nonsteroidal anti-inflammatory drugs (NSAID) are among the aggressive factors causing gastric ulcer. They cause oxidative damage in the gastric tissue and lead to intracellular calcium deposition. Lercanidipine is a calcium channel blocker derived from the third generation dihydropyridine. The aim of this study is to analyse the effect of lercanidipine on indomethacin-induced gastric ulcers. A total of 24 albino Wistar male rats were divided into four groups; those who received indomethacin 25 mg/kg (IND), 5 mg mg/kg lercanidipine +25 mg/kg indomethacin (LC-5), 10 mg/kg lercanidipine+25mg/kg indomethacin (LC-10) and healthy rats who received 0.5 mL distilled water. Six hours after the application of indomethacin, the animals were sacrificed by high dose thiopental sodium. The stomachs of the animals were excised to perform a macroscopic analysis and the ulcerous region was measured on millimeter paper. All the stomachs were subjected to a biochemical analysis. Macroscopic analysis revealed hyperaemia on the gastric surface of the indomethacin group. Ulcerous tissues formed by oval, circular or irregular mucosal defects in varying diameters and depths were observed on the whole surface of the stomach. Hyperaemia was lower and ulcerous region was smaller in groups LC-5 and LC-10 compared to IND group. Malondialdehyde and myeloperoxidase levels were significantly lower and total glutathione and cyclooxygenase-1 activity were higher in groups LC-5 and LC-10. Lercanidipine did not change the cyclooxygenase-2 activity. Lercanidipine in doses 10 mg/kg is more effective compared to 5 mg/kg. Lercanidipinine can be useful in the treatment of NSAID-induced gastric damage.

Comparison of anti-inflammatory efficacy of lercanidipine and Tanacetum parthenium with indomethacin in rats

Background: Inflammation can be classified as either acute or chronic. NSAIDs are the most commonly prescribed drugs worldwide, and mostly have adverse effects. Lercanidipine a CCB of (DHPs) blocks the mediators of inflammation and has additional anti-inflammatory potential. Tanacetum parthenium (Feverfew) extracts have also shown its anti-inflammatory effects in experimental studies. It was decided to study anti-inflammatory effects of Lercanidipine and Tanacetum parthenium which was compared with Indomethacin. The present study was aimed to evaluate and compare the anti-inflammatory effect of lercanidipine and Tanacetum parthenium with Indomethacin in rats.Methods: The study was conducted in the department of Pharmacology UPUMS, Saifai after getting approval from IAEC.A total of 24 animals divided into 4 groups of six (n=6) animals each group were used, and the anti-inflammatory effects of both drugs were evaluated by Carrageenan-induced Paw Edema Model by digital Plethysmometer in rats, drug administration was with the same frequency.Results: The result of the present study had shown that lercanidipine produced anti-inflammatory effect compared to Indomethacin, while its efficacy in reducing paw edema was better at 1st hour, 48 and 72 hours while at 2nd hour and 3rd hour Indomethacin had better efficacy. Tanacetum parthenium also decreased paw edema at 2nd, 3rd, 48 and 72 hour while at 1st hour no effect was seen. However, at 72 hours, shown good efficacy compared to lercanidipine and Indomethacin.Conclusions: Lercanidipine could be a promising anti-inflammatory drug in reducing the inflammation and edema. However, herbal drug (Tanacetum parthenium) has shown anti- inflammatory efficacy when compared with Indomethacin. Both drugs were found safe during our study.

Effects ofⅠ,ⅡCrystal and Amorphous Forms of Lercanidipine Hydrochloride on the Preparation / 中国药房

OBJECTIVE:To study the effects of Ⅰ,Ⅱ crystal and amorphous forms of lercanidipine hydrochloride on the preparation,and provide theoretical basis for its development and consistency evaluation. METHODS:X-ray powder diffraction (XRD),infrared spectrophotometry(IR)and differential scanning calorimetry(DSC)were adopted to identify the 3 crystal forms of lercanidipine hydrochloride. XRD was used to compare the effects of crushing,grinding,pressing technology,wetting granula-tion,adhesive solvents(water,ethanol)and drying temperature(50,60,70℃)on stability of 3 crystal forms of lercanidipine hy-drochloride;the dissolution in vitro in water,hydrochloride,pH 4.5 acetate buffer,pH 6.8 phosphate buffer were compared among 3 crystal forms of Lercanidipine hydrochloride tablet. RESULTS:XRD showed both Ⅰ,Ⅱ crystal forms had characteristic diffrac-tion peak with inconsistent 2 θ values,amorphous had no characteristic diffraction peak;IR showed 3 crystal forms had different absorption intensity and absorption peak number;DSC showed Ⅰ,Ⅱ crystal forms had obvious endothermic peak in 194.6 ℃, 207.3 ℃,respectively,amorphous had obvious endothermic peak in 86.1 ℃ and exothermic peak in 299.8 ℃. Crushing,grinding, pressing and drying temperature had no effects on the stability of 3 crystal forms;water had no effect on the stability of crystal in wetting granulation,ethanol may cause the change of Ⅰcrystal form. Except for the comparison between Ⅰ,Ⅱ crystal forms in hydrochloride (f2=68),the dissolution f2 of 3 crystal forms in 4 kinds of medium were lower than 50. CONCLUSIONS:XRD, IR,DSC methods can identify the 3 crystal forms of Lercanidipine hydrochloride tablet. When preparing lercanidipine hydrochlo-ride by Ⅰcrystal form,wetting granulation should avoid using ethanol as a adhesive solvent,instead of water. Different crystal forms can affect the dissolution in vitro of prepared Lercanidipine hydrochloride tablet.

Determination of lercanidipine in human plasma by an improved UPLC-MS/MS method for a bioequivalence study$ / 药物分析学报

An improved and reliable ultra-performance liquid chromatography/tandem mass spectrometry (UPLC–MS/MS) method has been developed and validated for the determination of lercanidipine in human plasma. Plasma samples with lercanidipine-d3 as an internal standard (IS) were prepared by solid phase extraction on Phenomenex Strata-X cartridges using 100 mL of human plasma. Chromatographic analysis was performed on UPLC BEH C18 (50 mm ? 2.1 mm, 1.7 mm) column under isocratic conditions. Linear calibration curves were obtained over a wide dynamic concentration range of 0.010–20.0 ng/mL. Matrix effect was assessed by post-column infusion, post-extraction spiking and standard-line slope methods. The mean extraction recovery was 4 94%for the analyte and IS. Inter-batch and intra-batch precision (%CV) across five quality controls was o 5.8%. Bioequivalence study was performed with 36 healthy sub-jects after oral administration of 10 mg of lercanidipine and the assay reproducibility was evaluated by reanalysis of 133 incurred samples.