Simple and effective high performance liquid chromatographic (HPLC) method was developed for estimation of Clindipine in drug free human drug free blank plasma. The internal standard used as Nifidipine (IS). The current method was used protein precipitating extraction of Clindipine from blank plasma. Separation was achieved on reversed-phase c18 column (25cm × 4.6mm, 5μ) and the detection was monitored by UV detector at 260 nm. The optimized mobile phase was used acetonitrile: 5mM potassium dihydrogen orthophosphate (pH 4.5), in the ratio of 60:40% v/v at a flow rate of 1.0 ml/min. This linearity was achieved in this method range of 10.0-125.0 ng/ml with regression coefficient range is 0.99. The present method is suitable in terms of precise, accurate and specific during the study. The simplicity of the method allows for application in laboratories that lack sophisticated analytical instruments such as LC-MS/MS or GC-MS/MS that are complicated, costly and time consuming rather than a simple HPLC-UV method. The present method was successfully applied for pharmacokinetic studies.
A study was conducted to compare the in vivo bioavailability of a generic metoprolol tablet preparation (Metoprolol) with that of the innovator product, Betaloc. Both preparations have a labeled dose of 100 mg metoprolol tartrate. Twelve healthy adult male volunteers participated in the study, which was conducted according to a standard two-way crossover design with a washout period of 1 week. The bioavailability was compared using the total area under the plasma level versus time curve (AUC0-infinity), peak plasma concentration (Cmax), and time to reach peak plasma concentration (Tmax). No statistically significant difference was observed between the logarithmically transformed AUC0-infinity values or the logarithmically transformed Cmax values of the two preparations. However, a statistically significant difference was observed between the Tmax values, but may not be therapeutically significant or important. Moreover, the 90% confidence interval (CI) for the ratio of the logarithmically transformed AUC0-infinity values of Metoprolol over those of Betaloc was calculated to be between 0.94 and 1.02, while that of Cmax was between 0.98 and 1.01, both of which are within the acceptable limit of 0.80-1.25. From the data obtained, it was also observed that a high proportion of our volunteers of Asian origin appeared to be poor metabolizers of metoprolol, which was consistent with what had been observed in our previous study of another preparation of metoprolol.
The growing momentum of several common life-style diseases such as myocardial infarction, cardiovascular disorders, stroke, hypertension, diabetes, and atherosclerosis has become a serious global concern. Recent developments in the field of proteomics offering promising solutions to solving such health problems stimulates the uses of biopeptides as one of the therapeutic agents to alleviate disease-related risk factors. Functional peptides are typically produced from protein via enzymatic hydrolysis under in vitro or in vivo conditions using different kinds of proteolytic enzymes. An array of biological activities, including antioxidative, antihypertensive, antidiabetic and immunomodulating has been ascribed to different types of biopeptides derived from various food sources. In fact, biopeptides are nutritionally and functionally important for regulating some physiological functions in the body; however, these are yet to be extensively addressed with regard to their production through advance strategies, mechanisms of action and multiple biological functionalities. This review mainly focuses on recent biotechnological advances that are being made in the field of production in addition to covering the mode of action and biological activities, medicinal health functions and therapeutic applications of biopeptides. State-of-the-art strategies that can ameliorate the efficacy, bioavailability, and functionality of biopeptides along with their future prospects are likewise discussed.
The intercalation of perindopril erbumine into Zn/Al-NO(3)-layered double hydroxide resulted in the formation of a host-guest type of material. By virtue of the ion-exchange properties of layered double hydroxide, perindopril erbumine was released in a sustained manner. Therefore, this intercalated material can be used as a controlled-release formulation.
CYP2D6 polymorphisms are well described in normal populations but there are few data on its clinical significance. We therefore investigated the influence of CYP2D6 polymorphism on steady-state plasma concentrations and apparent oral clearance of metoprolol in patients with cardiovascular diseases.
Poor aqueous solubility and unfavourable de-esterification of olmesartan medoxomil (a selective angiotensin II receptor blocker), results in low oral bioavailability of less than 26%. Improvement of oral bioavailability with prolonged pharmacodynamics activity of olmesartan in Wistar rats had been approached by nanoemulsification strategy in our previous article [Colloid Surface B, 115, 2014: 286]. In continuation to that work, we herewith report the biodistribution behaviour and 28-day repeated dose sub-chronic toxicity of olmesartan medoxomil nanoemulsion in Wistar rats following oral administration. The levels of olmesartan in collected biological samples were estimated using our validated LC-MS/MS technique. Our biodistribution study showed significantly higher brain concentrations of olmesartan (0.290 ± 0.089 μg/mL, 0.333 ± 0.071 μg/mL and 0.217 ± 0.062 μg/mL at 0.5, 2.0 and 8.0 h post dosing, respectively) when administered orally as nanoemulsion formulation as compared to the aqueous suspension. In addition, the olmesartan nanoemulsion was found to be safe and non-toxic, as it neither produced any lethality nor remarkable haematological, biochemical and structural adverse effects as observed during the 28-days sub-chronic toxicity studies in experimental Wistar rats. It is herewith envisaged that the developed nanoemulsion formulation approach for the delivery of olmesartan medoxomil via oral route can further be explored in memory dysfunction and brain ischemia, for better brain penetration and improved clinical application in stroke patients.