ผลของยาอีฟาวิเร็นซ์ต่อเภสัชจลนศาสตร์ของยาคีโตนาโซลในผู้ป่วยติดเชื้อเอชไอวี

200

ผลของอีฟาวิเร็นว์ต่อเภสัชจลศาสตร์ของคีโตโคนาโชลในผู้ป่วยติดเชื้อเอชไอวี

Thesis (M.Sc., Pharmacology)--Prince of Songkla University, 200

ผลของคีโตโคนาโซลต่อเภสัชจลนศาสตร์ของริสเพอริโดนในอาสาสมัครชายไทยสุขภาพปกติ : รายงานผลการวิจัยฉบับสมบูรณ์

Prince of Songkla Universit

Bioequivalence study of a generic Risperidone (Iperdal®) in healthy Thai male volunteers

The objective of this study was to compare the rate and extent of absorption of a generic risperidone (Iperdal®) with a reference formulation (Risperdal®) when given orally. The study was an open label, randomized, two-period, two-sequence,single dose cross-over design with a 2 weeks washout period in 16 healthy Thai male volunteers. Single oral dose of two 2-mg tablets of risperidone were administered and serial blood samples were collected from the antecubital vein before and at0.17, 0.33, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 and 48 hours post dose. Risperidone plasma concentrations were assayed using a validated High Performance Liquid Chromatographic (HPLC)-UV method modified from Avenosoet al. (2000). Pharamcokinetic parameters i.e. Cmax, AUC0à48 and Tmax were analyzed by noncompartment analysis. Variations of the data were analyzed by Two Way Analysis of Variance (ANOVA). Statistics were tested as stated in USP 28 guidelinefor bioequivalence study. The maximum concentration (Cmax, ng/ml) of risperidone for the innovator and the generic product were 31.11±17.24 (range 5.64-56.78) and 32.58±19.77 (range 5.29-84.56) ng/ml, respectively. The area under theplasma concentration-time curve (AUC0®48) of the innovator and the generic product were 160.64±152.89 (range 18.57- 550.32) and 144.03±127.37 (range 16.27-456.0) ng.hr/ml, respectively. The time to maximum concentration (Tmax) of theinnovator and the generic product were 0.97±0.41(range 0.5-2) and 1.02±0.32 (range 0.5-1.5) hr, respectively. The 90% confidence interval of the ratio of the ln-transformed of Cmax and AUC0à48 of both preparations were 89.39-112.99% and80.02-107.28% respectively which were within the acceptance range of 80.00-125.00%. Therefore, it can be concluded that both preparations used in this study are bioequivalent in terms of both the rate and extent of absorption

Cytotoxicity Screening of Plants of Genus Piper in Breast Cancer Cell Lines

Purpose: To examine whether seven species of plants of genus Piper possess anti-cancer effects.Methods: One normal breast and three breast cancer cell lines were used to test cytotoxic effects over a period of 72 h using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The dried plants were extracted with methanol and dichloromethane, and the effective extract isolated by crystallization, acid/base extraction and column chromatography techniques. Fragmented DNA was purified by phenol/chloroform/isoamyl alcohol.Results: Methanol and dichloromethane extracts of Piper retrofractum, Piper betle, especially Piper nigrum, exhibited strong effect on MDA-MB-468. When the crude extract of P. nigrum was then separated by column chromatography, fraction D showed activity against both MCF-7 and MDA-MB-468 cells. Fraction DE that was isolated from D demonstrated a highly cytotoxic effect with IC50 values of 8.33 ± 1.27 and 7.48 ± 0.57 μg/ml on MCF-7 and MDA-MB-468 cells, respectively. Furthermore, fraction DF exhibited a strong cytotoxic effect only on MCF-7 with IC50 value of 6.51 ± 0.39 μg/ml. DNA smears of MCF-7 and MDA-MB-468 cells treated with fraction DE and DF were observed within 7 days.Conclusions: These results indicate that the compounds isolated from P. nigrum, viz, DE and DF, have cytotoxic effect on breast cancer cell lines. These fractions could be promising agent for breast cancer treatment. Further studies on the isolation, structural and mechanism elucidation of the active compound are still needed being carried out.Keywords: Cytotoxicity, Breast cancer, P. nigrum, DNA fragmentatio

A Novel Antibiotic, Rhodomyrtone: Pharmacokinetic Studies in a Murine Model and Optimization and Validation of High-Performance Liquid Chromatographic Method for Plasma Analysis

Rhodomyrtone has indisputable and undeniable potential as a new antibiotic for antibiotic-resistant Gram-positive bacteria. Therefore, the main objective of this study was to determine the pharmacokinetics profiles of orally administered rhodomyrtone in rats. A reverse-phase HPLC-UV method was developed, optimized and validated for the analysis of rhodomyrtone concentrations in rat plasma. The retention time of papaverine and rhodomyrtone was 3.928 and 5.937 min, with no interference with the excipients used. The lower limit of quantification (LLOQ) of rhodomyrtone in the plasma sample was 0.04 μg/mL, the accuracy of rhodomyrtone at the LLOQ level ranged from 93.64 to 106.36%, precision was 6.59%, 80–120% for accuracy and <20% CV for precision. The calibration curve was linear at concentrations ranging from 0.04 to 128 µg/mL with a correlation coefficient (r) value of equal to or greater than 0.999. Sprague Dawley rats received a single dose of rhodomyrtone at 50 and 100 mg/kg. Blood samples were collected from tail veins. The peak plasma concentration was observed at 2 h, and the area under the curve of rhodomyrtone at 50 mg/kg and 100 mg/kg was 3.41 ± 1.04 and 7.82 ± 1.53 μg·h/mL, respectively. The results demonstrated linear pharmacokinetics characteristics at the studied dosage range. The plasma concentration of rhodomyrtone was above the minimal inhibition concentrations of several common pathogenic bacteria of medical importance. The proposed HPLC-UV method is fast, cost-effective, reliable and reproducible, and it is proposed for the routine analysis of rhodomyrtone

Seasonal and Geographic Variation in Alkaloid Content of Kratom (<i>Mitragyna speciosa</i> (Korth.) Havil.) from Thailand

The objective of this study was to obtain data on the distribution of alkaloids in kratom plants grown in Thailand. Two collections were performed, covering the southern, central, and northern regions of Thailand and different seasons. The contents of alkaloids, including mitragynine (MG), paynantheine (PAY), and speciogynine (SG), were determined using the validated HPLC method. The 134 samples in the first collection were collected from Nam Phu subdistrict, Ban Na San, Surat Thani, Thailand, during June and October 2019 and January 2020. The maximum mitragynine content was 4.94% w/w in June (late summer), and the minimum content was 0.74% w/w in October (rainy season). To expand the study area after kratom decriminalization, 611 samples were collected in June–August 2021, October–December 2021, and January–April 2022. The accumulation of MG ranged from 0.35 to 3.46% w/w, 0.31 to 2.54% w/w, and 0.48 to 2.81% w/w, respectively. The meteorological data supported the climate’s effect on alkaloid production. Soil analysis revealed the importance of Ca and Mg in promoting alkaloid production. Geographical locations played a role in the variation of MG in kratom leaves, but did not affect the color of leaf veins. In conclusion, the present study suggested that the alkaloid content in kratom diverges based on seasonal and geographical origin