Current Issue : January - March Volume : 2019 Issue Number : 1 Articles : 5 Articles
Piperine is an alkaloid isolated from Piper nigrum Linn., (family-Piperaceae) a natural bioenhancer and is known to enhance the bioavailability of the drugs by inhibiting cytochrome P450. In the present study, the effect of piperine was investigated on antihyperlipidemic properties of simvastatin (SV) and the effects were supported with measurement of plasma concentrations. The results confirm that piperine enhanced the antihyperlipidemic activity of simvastatin in tyloxypol induced hyperlipidemic rats. The co-administration of SV along with piperine showed a greater percent protection when compared to animals receiving SV alone at dose levels of 50, 75, 100 mg/kg. Test animals receiving 100 mg/kg of SV along with piperine at dose of 10 mg/kg showed a maximum reduction in cholesterol and triglycerides. From the study it was observed that the plasma concentration of SV was high during the 2nd h of the study, but maximum % protection was observed during the 4th h, this might be due to the conversion of SV to simvastatin hydroxyl acid an active metabolite in high concentration. The finding of present study confirmed that piperine could be used as bioenhancer when co-administered with simvastatin....
A sensitive and simple chromatography-tandem mass spectrometry (LC-MS/MS) method\nwas developed to evaluate memantine in rat plasma. Memantine and propranolol (internal standard)\nin rat plasma was extracted using a methanol precipitation method. The standard curve value was\n0.2â??1000 ng/mL and selectivity, linearity, inter-day and intra-day accuracy and precision were within\nacceptance criteria. Using this validated method, drug-drug interactions between memantine and\ncimetidine was measured following co-administration of memantine and cimetidine intravenously\nand orally. Plasma exposure of memantine was increased by 1.6- and 3.0-fold by co-medication\nwith cimetidine intravenously and orally, respectively. It suggested that the drug interaction\noccurred during the gut absorption process, which was consistent with the results showing that the\nintestinal permeability of memantine in the presence of cimetidine was 3.2-fold greater than that of\nmemantine alone. Inhibition of cimetidine on hepatic elimination of memantine rather than renal\nexcretion was also attributed to the drug-drug interaction between memantine and cimetidine, which\nexplained the decreased clearance of memantine by co-medication with cimetidine. In conclusion,\nthe newly developed simple and sensitive LC-MS/MS analytical method was applied to investigate\nthe pharmacokinetic drug-drug interactions of memantine. Plasma exposure of memantine by\nco-administration with cimetidine was increased because of its enhanced intestinal permeability and\nthe decreased metabolic activity of memantine....
This study examined the effects of esomeprazole on aceclofenac pharmacokinetics and\ngastrointestinal complications in rats. Aceclofenac alone, or in combination with esomeprazole,\nwas orally administered to male Sprague-Dawley rats. Plasma concentrations of aceclofenac,\nits major metabolite diclofenac, and esomeprazole were simultaneously determined by a novel liquid\nchromatography-tandem mass spectrometry method. Gastrointestinal damage was determined by\nmeasuring ulcer area and ulcer lesion index of the stomach. Oral administration of aceclofenac\ninduced significant gastric ulceration, which was inhibited by esomeprazole administration.\nFollowing concurrent administration of aceclofenac and esomeprazole, overall pharmacokinetic\nprofiles of aceclofenac and metabolic conversion to diclofenac were unaffected by esomeprazole.\nAceclofenac metabolism and pharmacokinetics were not subject to significant food effects, whereas\nbioavailability of esomeprazole decreased in fed compared to fasting conditions. In contrast,\nthe pharmacokinetics of aceclofenac and esomeprazole were significantly altered by different dosing\nvehicles. These results suggest that co-administration of esomeprazole with aceclofenac may reduce\naceclofenac-induced gastrointestinal complications without significant pharmacokinetic interactions.\nThe optimal combination and clinical significance of the benefits of the combination of aceclofenac\nand esomeprazole need to be further evaluated....
DA-9805 is a botanical anti-Parkinsonâ??s drug candidate formulated from ethanol extracts\nof the root of Bupleurum falcatum, the root cortex of Paeonia suffruticosa, and the root of Angelica\ndahurica. The pharmacokinetics (PKs) and brain distribution of active/representative ingredients\nof DA-9805, Saikosaponin a (SSa; 1.1â??4.6 mg/kg), Paeonol (PA; 14.8â??59.2 mg/kg), and Imperatorin\n(IMP; 1.4â??11.5 mg/kg) were evaluated following the intravenous or oral administration of each\npure component and the equivalent dose of DA-9805 in rats. All three components had greater\ndose-normalized areas under the plasma concentration-time curve (AUC) and slower clearance with\nhigher doses, following intravenous administration. By contrast, dose-proportional AUC values of\nSSa, PA, and IMP were observed following the oral administration of each pure component (with\nthe exception of IMP at the highest dose) or DA-9805. Compared to oral administration of each\npure compound, DA-9805 administration showed an increase in the AUC of SSa (by 96.1â??163%) and\nPA (by 155â??164%), possibly due to inhibition of their metabolism by IMP or other component(s) in\nDA-9805. A delay in the absorption of PA and IMP was observed when they were administered as\nDA-9805. All three components of DA-9805 showed greater binding values in brain homogenates\nthan in plasma, possibly explaining why the brain-to-plasma ratios were greater than unity following\nmultiple oral administrations of DA-9805. By contrast, their levels in cerebrospinal fluid were\nnegligible. Our results further our understanding of the comprehensive PK characteristics of SSa, PA,\nand IMP in rats and the comparative PKs between each pure component and DA-9805....
Methyl 3-amino-6-methoxythieno [2,3-b] quinoline-2-carboxylate (PU-48) is a novel\ndiuretic urea transporter inhibitor. The aim of this study is to investigate the profile of plasma\npharmacokinetics, tissue distribution, and excretion by oral dosing of PU-48 in rats. Concentrations\nof PU-48 within biological samples are determined using a validated high performance liquid\nchromatography-tandem mass spectrometry (LC-MS/MS) method. After oral administration of\nPU-48 (3, 6, and 12 mg/kg, respectively) in self-nanomicroemulsifying drug delivery system\n(SNEDDS) formulation, the peak plasma concentrations (Cmax), and the area under the curve ......... were increased by the dose-dependent and linear manner, but the marked different of\nplasma half-life (t1/2) were not observed. This suggests that the pharmacokinetic profile of PU-48\nprototype was first-order elimination kinetic characteristics within the oral three doses range in rat\nplasma. Moreover, the prototype of PU-48 was rapidly and extensively distributed into thirteen\ntissues, especially higher concentrations were detected in stomach, intestine, liver, kidney, and bladder.\nThe total accumulative excretion of PU-48 in the urine, feces, and bile was less than 2%. This research\nis the first report on disposition via oral administration of PU-48 in rats, and it provides important\ninformation for further development of PU-48 as a diuretic drug candidate....
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