Current Issue : April - June Volume : 2018 Issue Number : 2 Articles : 5 Articles
Melatonin possesses potential efficacy in perinatal brain injuries, and has been proposed as\nadjunctive pharmacological therapy in combination with hypothermia in the clinical setting. However,\nthe pharmacokinetics of melatonin in preterm and term newborns is still unknown. The aim of this\nstudy was to analyze the pharmacokinetics of melatonin after intragastric administration in preterm\ninfants. Preterm newborns were enrolled 24ââ?¬â??72 h after birth, and randomly assigned to three groups\nreceiving a single bolus of 0.5 mgÃ?·kgâË?â??1 melatonin, or 3 boluses of 1 or 5 mgÃ?·kgâË?â??1 of melatonin at 24-h\nintervals. Blood samples were collected before and at selective times after melatonin administration.\nThe half-life of melatonin in plasma ranged from 7.98 to 10.94 h, and the area under the curve\n(AUC) from 10.48 to 118.17 Ã?¼gÃ?·mLâË?â??1Ã?·hâË?â??1. Our results indicate a different pharmacokinetic profile\nin premature newborns, compared to adults and experimental animals. The high peak plasma\nconcentrations and the long half-life indicate that in the neonatal clinical setting, it is possible to\nobtain and maintain high serum concentrations using a single administration of melatonin repeated\nevery 12/24 h....
The purpose of the present study was to determine whether caffeine modifies the\npharmacokinetics and pharmacodynamics of (S)-ketoprofen following oral administration in a\ngout-type pain model. 3.2 mg/kg of (S)-ketoprofen alone and combined with 17.8 mg/kg of\ncaffeine were administered to Wistar rats and plasma levels were determined between 0.5 and\n24.0 h. Additionally, antinociception was evaluated based on the protocol of the PIFIR (pain-induced\nfunctional impairment in the rat) model before blood sampling between 0.5 and 4.0 h. Significant\ndifferences in Cmax, AUC0-24, and AUC0-âË?ž values were observed with caffeine administration\n(p < 0.05). Also, significant differences in Emax, Tmax, and AUC0-4 values were determined when\ncomparing the treatments with and without caffeine (p < 0.05). By relating the pharmacokinetic\nand pharmacodynamic data, a counter-clockwise hysteresis loop was observed regardless of the\nadministration of caffeine. When the relationship between AUCe and AUCp was fitted to the\nsigmoidal Emax model, a satisfactory correlation was found (R2 > 0.99) as well as significant differences\nin Emax and EC50 values (p < 0.05). With caffeine, Emax and EC50 values changed by 489.5% and\n695.4%, respectively. The combination studied represents a convenient alternative for the treatment\nof pain when considering the advantages offered by using drugs with different mechanisms of action....
The purpose of this study was to evaluate the potential of micelle to change the pharmacokinetics of quercetin (QUT), with a\nprimary goal of enhancing its oral bioavailability. QUT-loaded methoxy poly(ethylene glycol)-...
Understanding snake venom pharmacokinetics is essential for developing risk assessment\nstrategies and determining the optimal dose and timing of antivenom required to bind all venom\nin snakebite patients. This review aims to explore the current knowledge of snake venom\npharmacokinetics in animals and humans. Literature searches were conducted using EMBASE\n(1974ââ?¬â??present) and Medline (1946ââ?¬â??present). For animals, 12 out of 520 initially identified studies met\nthe inclusion criteria. In general, the disposition of snake venom was described by a two-compartment\nmodel consisting of a rapid distribution phase and a slow elimination phase, with half-lives of\n5 to 48 min and 0.8 to 28 h, respectively, following rapid intravenous injection of the venoms\nor toxins. When the venoms or toxins were administered intramuscularly or subcutaneously,\nan initial absorption phase and slow elimination phase were observed. The bioavailability of\nvenoms or toxins ranged from 4 to 81.5% following intramuscular administration and 60% following\nsubcutaneous administration. The volume of distribution and the clearance varied between snake\nspecies. For humans, 24 out of 666 initially identified publications contained sufficient information\nand timed venom concentrations in the absence of antivenom therapy for data extraction. The data\nwere extracted and modelled in NONMEM. A one-compartment model provided the best fit, with an\nelimination half-life of 9.71 Ã?± 1.29 h. It is intended that the quantitative information provided in this\nreview will provide a useful basis for future studies that address the pharmacokinetics of snakebite\nin humans....
Icariin is one of the predominant flavonoids contained in Herba Epimedii (Yin-yang-huo in Chinese), a well-known Chinese\nmedicine for the treatment of cancers and immune system diseases. Although Herba Epimedii has been widely used in China and\nthere are so many and various research reports on the herbal drug and its main flavones, very limited data is available on the tissue\ndistribution and biotransformation of icariin. In the present study, a liquid chromatographic method combined with electrospray\nionization tandem mass spectrometry was developed to quantify the concentration of icariin in rat plasma and various tissues\ncollected at different time points after oral administration of the total flavonoid extract of Herba Epimedii at a dose of 0.69 g/kg\n(corresponding to 42mg/g icariin). Biological samples were processed by simple protein precipitation. Genistein was chosen as\ninternal standard. The method was successfully applied to plasma pharmacokinetic and tissue distribution studies of icariin in\nrat. As a result, it was worth noting that the tissue distribution characteristics of icariin exhibited a significant gender difference.\nMoreover, in vivo metabolism of icariin was also investigated. A total of 11 potential metabolites were found in rat feces collected in\ndifferent time periods after oral and intramuscular administration of icariin. In vivo metabolic pathwayswere involved in hydrolysis,\ndemethylation, oxidation, and conjugation.The preclinical data would be useful for fully understanding in vivo disposition of this\ncompound and interpreting the mechanism of its biological response....
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