ABSTRACT
OBJECTIVE: Regardless of having desired therapeutic properties many of the recently approved drugs are removed from the developmental pipeline for their clinical use due to low solubility and permeability. Conventional dosage forms are found relatively unsuitable for achieving desired pharmacokinetic and pharmacodynamics profiles.Cilnidipine is 1,4 dihydropyridine derivative calcium channel blocker used for the treatment of hypertension. METHOD: The aim and objective of this study was to develop a precise and significant method in LC-MS/MS for quantification of pharmacokinetic parameters of a cilnidipine loaded self microemulsifying drug delivery system in rat plasma and simultaneously assessed pharmacodynamic characters in comparison with the marketed cilnidipine tablet. Another potential aim of this study is to reduce the dose of the drug in order to counter the dose-dependent toxicities related to chronic use. In the present study, the parent and product ion of cilnidipine was m/z 491.3\237.1. RESULT: The plasma was extracted by protein precipitation technique. The calibration standard concentrations were 1.875, 3.75, 7.50, 15.00, 30.00, 60.00 ng/ml and LLOQ, Low-quality control, Middle-quality control and High-quality control were 1.87, 5.62,22.50,45.00ng/ml respectively. The mobile phase composition was 0.1% formic acid in Milli Q water with 10mM Ammonium acetate as an aqueous solvent and 0.1% formic acid in methanol as an organic solvent. Following oral administration of optimized formulation Cmax (peak plasma concentration) was achieved 21.02±3.17 ng/ml at 0.866 ± 0.11 hr. (Tmax), whereas in the case of marketed tablet Cmax (peak plasma concentration) was achieved 10.16±0.89 ng/ml at 0.93±0.11 hr (Tmax). DISCUSSION: The in-vivo characterizations of the optimized SMEDDS showed significantly better pharmacokinetic parameters in Wistar rats and showed almost 2.4 times enhanced relative bioavailability as compared to the marketed tablet of Cilnidipine which was observed to be correlating to our findings with Non-invasive blood pressure parameter of Wistar rats.
ABSTRACT
BACKGROUND: Urticaria is a clinical condition characterized by the appearance of wheals (hives), angioedema, or both. Over the last several decades, a better understanding of the mechanisms at play in the immunopathogenesis of urticaria has underscored the existence of numerous urticaria subtypes. Separating the different kinds of urticaria explicitly helps find the best detection method for the management of this skin disorder. Subtypes of urticaria also include both spontaneous and physical types. The conventional ones include spontaneous urticaria, constituting both acute and chronic urticaria. Therefore, a broad and effective therapy is essential for the diagnosis and treatment of urticaria. METHODS: To understand the immunopathogenesis of urticaria, various databases, including PubMed, Scopus, and Web of Science, were used to retrieve original articles and reviews related to urticaria. While information on several clinical trials were obtained from clinicaltrials.gov database. RESULTS: This article highlights the immunopathogenesis involved in the intricate interaction between cellular infiltration, immune reactions, coagulation cascades, and autoantibodies that underlie urticaria's pathophysiology. CONCLUSION: The recent progress in understanding urticaria can help to understand the intricate characteristics in the immunopathogenesis of urticaria and could play a beneficial role in the management of urticaria.
Subject(s)
Cytokines , Histamine , Urticaria , Humans , Urticaria/immunology , Histamine/immunology , Cytokines/immunology , AnimalsABSTRACT
Background: Systemic arterial hypertension, which is associated with an increased risk of cardiovascular disease(CVD), is the most significant modifiable risk factor for mortality and morbidity worldwide. WHO has recognized Unanipathy as an alternate system of medicine. The aim of the present study is to investigate the anti-hypertensive activity of some selected unani formulations using L-NAME model. Method: Group I or hypertensive control group: L-NAME administered for 7 days and left for the next 7 days; Group II or KASgroup: L-NAME administered (i.p) for 7 days and L-NAME + KAS (1000 mg/kg b.w) for the next 7 days; Group III or DMM group: L-NAME administered (i.p) for 7 days and L-NAME + DMM (2000 mg/kg b.w) for the next 7 days; Group IV or MSR group: L-NAME administered (i.p) for 7 days and L-NAME + MSR (300 mg/kg b.w) for the next 7 days; Group V or HJ group: L-NAME administered (i.p) for 7 days and L-NAME + HJ (113 mg/kg b.w) for the next 7 days; Group VI or KGS group: L-NAME administered (i.p) for 7 days and L-NAME +KGS (2000 mg/kg b.w) for the next 7 days. Non-invasive systolic blood pressure and RR-interval (ECG) was measured. Plasma was investigated forsodium, potassium, nitrite, ANP, adrenaline, noradrenaline and aldosterone on day 0, 7 and 14 using LC-MS/MS. Result: Treatment showed a non-significant lowreduction in SBP (systolic blood pressure) of KAS, MSR and HJ while that of DMM was quite significant (p < 0.05), but in the case of KGS, SBP increased. DMM on day 14 significantly (p < 0.05) reduced plasma nitrite while no significant plasma Na+ was noted. In the case of both DMM and KGS, potassium increased significantly (p < 0.05) on day 14. No significant changes in plasma ANP and aldosterone was observed against DMM and KGS while blood levels of adrenaline and noradrenaline significantly (p < 0.05) changed. No significant change in body weight was found. Conclusions: L-NAME KAS, MSR and HJ showed no change in SBP while DMM showed a significant reduction in SBP with decreased plasma nitrite. Probably, DMM may have anti-hypertensive activity mediated through NO inhibition while KGS may involve central sympathomimetic action.