ABSTRACT
To evaluate the anti-arthritic effects of Polygonatum kingianum rhizome extract using both in vitro and in vivo models. Methods: Lipopolysaccharide-induced RAW 264.7 macrophages were treated with an ethanol extract of Polygonatum kingianum rhizomes at different concentrations to determine nitric oxide and prostaglandin E2 (PGE2) production. For in vivo study, Polygonatum kingianum ethanol extract was further investigated for its antiinflammatory effect in a mouse model with collagen antibodyinduced arthritis. Phytochemical study of Polygonatum kingianum ethanol extract was also performed. Results: Saponins (142 mg/g total yield) was the main component in the Polygonatum kingianum ethanol extract. 5a,8a-ergosterol peroxide, (E,E)-9-oxooctadeca-10,12-dienoic acid and 3-(2'- hydroxy-4'-methoxy-benzyl)-5,7-dihydroxy-8-methyl-chroman-4- one were isolated from the extract. Polygonatum kingianum ethanol extract exhibited potential anti-inflammatory effects by inhibiting nitric oxide and PGE2 production in RAW 264.7 cells in a dosedependent manner. The level of arthritis in mice with collagen antibody-induced arthritis was significantly reduced (P0.01) after treatment with Polygonatum kingianum ethanol extract, particularly at a dose of 1 000 mg/kg body weight. Besides, the extract demonstrated the regulatory effects on serum tumor necrosis factoralpha, interleukin-6, and interleukin-10 in treated mice. Conclusions: Polygonatum kingianum ethanol extract has beneficial effects on inflammatory cytokine regulation and PGE2 inhibition in an experimental mouse model with collagen antibody-induced arthritis. The phytochemical screening reveals that the saponin, as the main component, and sterols (daucosterol and 5a,8a-ergosterol peroxide) from Polygonatum kingianum ethanol extract may contribute to its promising in vitro and in vivo anti-inflammatory activities.
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Aims: To evaluate the value of therapeutic drug monitoring (TDM) of vancomycin in clinical practice. Methods: To review retrospectively on 292 hospital cases (111 females, 181 males) treated with vancomycin, July to October 2014, at ChoRay Hospital. The main evaluating parameters were TDM criteria for vancomycin (dose, dosing interval, times of monitoring), trough level, dose adjustment, renal function follow-up, minimum inhibitory concentration of infectious agents, clinical response. Results: Two hundred seventy-five patients (94.2%) received routine dose of 1 g vancomycin per IV infusion time. Dosing interval was given correctly to estimated glomerular filtration rate (eGFR) level 80.8% (235/291). The 1st monitoring after 9th dose was in 139 cases (47.6%). Trough level was lower than 10 mg/L in 86 patients (29.5%), higher than 20 mg/L in 96 (32.9%), and 110 in optimal range 10-20 mg/L (37.7%). Age and eGFR were 2 independent predictors for trough level. Dose adjustment were done in 6.9% (6/86) patients ≤ 10 mg/L, 20.8% (20/96) ones >20 mg/L, and 11.8% (13/110) ones 10-20 mg/L. Vancomycin concentrations in young patients were lower than those in elderly ones with OR = 5.9 [95%CI: 2.6 – 14.0], p = 0.0001. Response sensitivity was 69.3% (13/19) for dose reduction, and 83.3% (5/6) for dose increase. Dose adjustment did not make change in trough level compared to unadjusted ones. Nephrotoxicity rate was found as 8.4%. Treatment failure was 50% in patients with trough concentration/minimum inhibition concentration ratio ≤ 10 compared to 15% in ones with higher ratio > 10, p = 0.034. The failure rate was highest in patients received vancomycin ≤ 7 days (22/70: 31.4%), OR: 4 (2.0-7.7) p=0.002. The clinical AUC/MIC ratio cut-off, 190 mg/L/day, had 75.9% and 66.7%, respectively for sensitivity and specificity to predict the success result in treatment. Conclusion: The criteria of TDM on vancomycin were not applied strictly, especially for dosing intervals, dosing adjustment and follow-up thereafter. The clinical pharmacodynamics of vancomycin is dependent on both concentration and duration of treatment.
ABSTRACT
The present study describes the development and validation of a simple, sensitive, and specific liquid chromatography-mass spectrometry (LC-MS) analytical method used for the co-quantification of artesunate (ARS) and its active metabolite, dihydroartemisinin (DHA), in human plasma, using artemisinin (ARN) as an internal standard. The liquid-liquid extraction of samples was carried out using dichloromethane and tert.-methyl butyl ether (at a ratio of 8:2 v/v) and then evaporated to dryness by a stream of nitrogen gas at room temperature. Chromatographic separation and mass analysis were performed on the Agilent 1100 Series Liquid Chromatography/Mass Spectrometer Detector Trap system, using electrospray ionization as an interface. The stationary phase was an Elipse XDB-C18 column. The mobile phase contained acetonitrile and 0.003 M glacial acetic acid at a ratio of 62:38 (v/v) delivered at a flow rate of 0.5 ml per minute. Positive ion mode was selected to detect extracted ions at m/z 407 and 261 for ARS, at m/z 307 and 261 for DHA, and at m/z 305 for ARN. The retention times for alpha-DHA, ARS, beta-DHA, and ARN were 6.6, 8.0, 9.2, and 10.8 minutes, respectively, and the total chromatography run time was 12 minutes. The limit of detection (LOD) was 2 ng/ml while the limit of quantification (LOQ) was 10 ng/ml for both ARS and DHA. In order to address any complications caused by the spontaneous non-catalytic breakdown of ARS to DHA, two calibration curves were prepared separately for both analytes. These graphs were found to be linear over the range of 10 to 3,200 ng/ml (r2 > 0.99). The recoveries at concentrations of 100, 200, 400, and 800 ng/ml were 108, 106, 91, and 89%, respectively, for ARS and were 112, 95, 80, and 86%, respectively, for DHA. For ARN, the recoveries were 119, 119, and 90% for concentrations of 200, 400, and 800 ng/ml, respectively. ARS working solutions were not stable after two months of storage at 4 degrees C or after 21 days at room temperature. This newly developed LC-MS method was then applied for measuring of ARS and DHA concentrations in a healthy volunteer having received oral ARS at 200 mg once daily for 5 consecutive days. There was no decline in ARS concentration after repeated doses and the C(ss-max-average) for DHA was found to be 703 +/- 94 ng/ml at t(ss-max) of 2 h.
Subject(s)
Antimalarials/blood , Area Under Curve , Artemisinins/blood , Chromatography, Liquid , Half-Life , Humans , Mass Spectrometry , Metabolic Clearance Rate , Sensitivity and SpecificityABSTRACT
The objective of this study was to investigate the pharmacokinetics of mefloquine (MQ) when given as 750 mg at two different times in combination regimens with dihydroartemisinin (DHA) in patients with acute uncomplicated falciparum malaria. A total of 12 Vietnamese patients (6 in each group) were randomized to receive two MQ-DHA regimens as follows: regimen-A: an initial oral dose of 300 mg DHA, followed by 750 mg MQ and 300 DHA 6 and 24 hours later; regimen-B: an initial dose of 300 mg DHA, followed by 300 mg DHA and 750 mg MQ at 24 hours. Both combination regimens were well tolerated. All patients responded well to treatment with no recrudescence during a 42 day follow-up period. The pharmacokinetics of MQ following both regimens were similar but pooled data from both groups suggest that the kinetics of MQ was different from that observed in Vietnamese healthy subjects reported in a previous study. The median (95% CI) time period for maintenance of whole blood MQ concentrations above 500 ng/ml was 16 (0-24) days. It was concluded that since no pharmacokinetic drug interaction was observed, MQ dose given 24 hours after an initial dose of DHA is a preferable combination treatment regimen with regard to patient compliance.