Current Issue : October - December Volume : 2019 Issue Number : 4 Articles : 5 Articles
This study investigated the pharmacokinetics of tofacitinib in rats and the effects of first-pass\nmetabolism on tofacitinib pharmacokinetics. Intravenous administration of 5, 10, 20, and 50 mg/kg\ntofacitinib showed that the dose-normalized area under the plasma concentration-time curve from\ntime zero to infinity (AUC) was significantly higher at 50 mg/kg than at lower doses, a difference\npossibly due to saturation of the hepatic metabolism of tofacitinib. Oral administration of 10, 20, 50,\nand 100 mg/kg tofacitinib showed that the dose-normalized AUC was significantly higher at 100\nmg/kg than at lower doses, a difference possibly due to saturation of the intestinal metabolism of\ntofacitinib. Following oral administration of 10 mg/kg tofacitinib, the unabsorbed fraction from the rat\nintestine was 3.16% and the bioavailability (F) was 29.1%. The AUC was significantly lower (49.3%)\nafter intraduodenal, compared to intraportal, administration, but did not differ between intragastric\nand intraduodenal administration, suggesting that approximately 46.1% of orally administered\ntofacitinib was metabolized through an intestinal first-pass effect. The AUC was also significantly\nlower (42%) after intraportal, compared to intravenous, administration, suggesting that the hepatic\nfirst-pass effect on tofacitinib after entering the portal vein was approximately 21.3% of the oral\ndose. Taken together, these findings suggest that the low F of tofacitinib is due primarily to intestinal\nfirst-pass metabolism....
Ginseng has been used to alleviate age-related dementia and memory deterioration for\nthousands of years. This study investigated the protective effect of red ginseng saponins against\nscopolamine-induced cerebral injury. Meanwhile, pharmacokinetics of ginsenosides in normal\nand scopolamine-treated rats were compared. After scopolamine injection, glutathione, catalase\nand superoxide dismutase levels were significantly decreased when compared with control group.\nCompared with SA group, pretreatment of rats with red ginseng saponins could increase glutathione,\ncatalase and superoxide dismutase level. Treatment with red ginseng saponins significantly decreased\nmalondialdehyde level. In the pharmacokinetic analysis, a pattern recognition analysis method was\nused to investigate the pharmacokinetics of the absorbed compounds in blood. The pharmacokinetic\nparameters of Rg1, Rg2, Rh3, Rg5 and Rk1 in model group had higher area under the curve (AUC),\nmean residence time (MRT) and peak plasma concentration (Cmax) values; area under the curve\n(AUC) values and peak plasma concentration (Cmax) of model group was significantly different\nfrom that of normal group (p < 0.05). The Cmax value of Rk3, Rh1, Rh2 and Rh4 in model group\nwas higher than normal group, but their AUC values were not significantly different. There was no\nsignificantly difference in time at Cmax (Tmax), AUC and Cmax values of Rb1, Rb2 Re, Rc, Rd and Rf\nbetween the model and normal group. 16 ginsenosides were grouped into three separate clusters\naccording to principal component analysis (PCA) score plot based on pharmacokinetic data. The\nresults suggested red ginseng saponins have significant protective effect against scopolamine-induced\nmemory deficit and scopolamine-induced rats could lead to the changes of pharmacokinetic behaviors\nof ginsenosides....
(1) Background: Rhubarb anthraquinones-a class of components with neuroprotective\nFunction-can be used to alleviate cerebral ischemia reperfusion injury. (2) Methods: The three\npharmacodynamic indicators are neurological function score, brain water content, and cerebral\ninfarction area; UPLC-MS/MS was used in pharmacokinetic studies to detect plasma concentrations\nat different time points, and DAS software was used to calculate pharmacokinetic parameters in\na noncompartmental model. (3) Results: The results showed that the pharmacodynamics and\npharmacokinetics of one of the five anthraquinone aglycones could be modified by the other four\nanthraquinones, and the degree of interaction between different anthraquinones was different.\nThe chrysophanol group showed the greatest reduction in pharmacodynamic indicators comparing\nwith other four groups where the rats were administered one of the five anthraquinones, and there\nwas no significant difference between the nimodipine group. While the Aloe-emodin + Physcion\ngroup showed the most obvious anti-ischemic effect among the groups where the subjects were\nadministered two of the five anthraquinones simultaneously. Emodin, rhein, chrysophanol, and\nphyscion all increase plasma exposure levels of aloe-emodin, while aloe-emodin lower their plasma\nexposure levels. (4) Conclusions: This experiment provides a certain preclinical basis for the study\nof anthraquinone aglycones against cerebral ischemia and a theoretical basis for the study of the\nmechanism of interaction between anthraquinones....
GC20, a novel soluble bis-chelated gold(I)-diphosphine compound, has been reported\nas a promising anticancer candidate. Assessing the pharmacokinetic properties of GC20 is critical\nfor its medicinal evaluation. First, a sensitive and specific liquid chromatography tandem mass\nspectrometry (LC-MS/MS) was developed and well validated to determine GC20 in rat plasma\nand rat tissue homogenate after one step protein precipitation. Chromatographic separation was\nachieved on an Angilent ZORBAX-C18 column (3.5 microm, 2.1*50 mm) with gradient elution and\nmass spectrometry was performed on a triple quadrupole in positive ion mode using an electrospray\nionization source. This method was then applied to investigate the pharmacokinetics and tissue\ndistribution of GC20 in rats after intravenous administration. The results showed that the plasma\nexposure of GC20 in vivo increased with increasing doses after a single dose. However, after multiple\ndoses, a significant accumulation and a saturation at elimination were observed for GC20 in rats.\nMoreover, after intravenous administration, GC20 was widely distributed in various tissues, with the\nhighest levels in the lung, spleen, liver, and pancreas, followed by the kidney and heart, while the\nlowest level was found in the brain. This is the first report on the pharmacokinetic properties of GC20....
Botulinum neurotoxins (BoNT) are potential biothreat agents due to their high lethality,\npotency, and ease of distribution, thus the development of antitoxins is a high priority to the US\ngovernment. This study examined pre-clinical pharmacokinetic studies in rats of four oligoclonal\nanti-BoNT mAb-based therapeutics (NTM-1631, NTM-1632, NTM-1633, NTM-1634) for five BoNT\nserotypes (A, B, E, C, and D). NTM-1631, NTM-1632, and NTM-1633 each consist of three IgG1\nmAbs, each with a distinct human or humanized variable region which bind to distinct epitopes\non BoNT serotype A, B, or E respectively. NTM-1634 consists of four human immunoglobulin G1\n(IgG1) mAbs binding BoNT C/D mosaic toxins. The mechanism of these antitoxins requires that three\nantibodies simultaneously bind toxin to achieve rapid clearance. Rats (total 378) displayed no adverse\nclinical signs attributed to antibody treatment from any of the antitoxins. Pharmacokinetic evaluation\ndemonstrated that the individual mAbs are slowly eliminated, exhibiting dose-dependent exposure\nand long elimination half-lives ranging from 6.5 days to 10 days. There were no consistent differences\nobserved between males and females or among the individual antibodies in each formulation in\nhalf-life. Anti-drug antibodies (ADA) were observed, as expected for human antibodies administered\nto rats. The results presented were used to support the clinical investigation of antibody-based\nbotulism antitoxins....
Loading....