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Journal of Pharmaceutical and... Feb 2011A selective, rapid and sensitive method for the quantitation of 4-hydroxy-anethole trithione (ATX) in human plasma based on high-performance liquid chromatography-tandem...
A selective, rapid and sensitive method for the quantitation of 4-hydroxy-anethole trithione (ATX) in human plasma based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed and validated. Paracetamol was used as the internal standard (I.S.). After liquid-liquid extraction of 500 μL plasma with ethyl acetate, ATX and the I.S. were chromatographed on an Inertsil(®) ODS-3 column. The mobile phase was consisted of methanol-water (75:25, v/v) with a flow rate of 0.25 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source. The calibration curve was linear over the range of 0.452-603 ng/mL (r(2)≥0.99) with a lower limit of quantitation (LLOQ) of 0.452 ng/mL. The intra- and inter-day precision (relative standard deviation, R.S.D.) values were below 13% and the accuracy (relative error, R.E.) was from -2.7% to -7.5% at three quality control levels. The assay herein described was successfully applied to a pharmacokinetic study of anethole trithione (ATT) tablet in healthy volunteers after oral administration.
Topics: Anethole Trithione; Calibration; Chromatography, High Pressure Liquid; Drug Stability; Humans; Male; Quality Control; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Tablets; Tandem Mass Spectrometry
PubMed: 20980118
DOI: 10.1016/j.jpba.2010.09.037 -
Journal of Pharmaceutical and... Jul 2008A simple, selective and reproducible high-performance liquid chromatographic (HPLC) method via enzymatic hydrolysis of glucuronide conjugates of 4-hydroxy-anethole...
A simple, selective and reproducible high-performance liquid chromatographic (HPLC) method via enzymatic hydrolysis of glucuronide conjugates of 4-hydroxy-anethole trithione (ATX) was established for simultaneous determination of ATX. Human plasma samples were hydrolyzed by beta-glucuronidase and followed by subsequent extraction with cyclohexane-isopropanol (95:5, v/v) using mifepristone as the internal standard. Chromatography was carried out on a reverse phase C(18) column (250 mm x 4.6 mm, 5 microm) and kept at 30 degrees C, with UV detection set at 346 nm. The mobile phase consisted of a mixture of methanol and water (75:25, v/v), at a flow rate of 1 ml/min. It was validated and proved to be linear in the range of 20-1500 ng/ml, with the regression equation Y = 0.0016C-0.0069, r=0.9992. And the limit of quantification (LOQ) concentration in plasma was 20 ng/ml. The absolute recoveries of ATX at three concentrations were 32.04, 38.95 and 44.06% and the relative recoveries were 104.80, 102.53 and 107.04%, which showed that the analytical method was sensible, accurate and reproducible. The method was utilized on a double-blind, randomized, single dose, two period, and crossover bioequivalence study of ATT tablets produced by different companies in 20 healthy male Chinese subjects, with a washout between every two periods. Blood samples were collected over each period of 10h and various pharmacokinetic parameters were determined. Natural log-transformed values were compared by analysis of variance followed by classical 90% confidence interval for C(max), AUC(0-t) and AUC(0-infinity) and was found to be within the range, which indicated that the two products were bioequivalence.
Topics: Anethole Trithione; Area Under Curve; Chromatography, High Pressure Liquid; Drug Stability; Glucuronidase; Humans; Hydrolysis; Therapeutic Equivalency
PubMed: 18353592
DOI: 10.1016/j.jpba.2008.01.044 -
Analytica Chimica Acta Jul 2007A rapid, sensitive and reliable high performance liquid chromatographic method coupled with tandem mass spectrometry via electrospray ionization (ESI) source... (Clinical Trial)
Clinical Trial
A rapid, sensitive and reliable high performance liquid chromatographic method coupled with tandem mass spectrometry via electrospray ionization (ESI) source (HPLC-MS/MS) has been developed and validated for the determination of anethole trithione (ATT) in human plasma. Diazepam was employed as the internal standard (IS). Sample extracts following liquid-liquid extraction were injected into the HPLC-MS/MS system. The analyte and IS were eluted isocratically on a C18 column, with a mobile phase consisting of methanol and aqueous ammonium acetate solution (5 mM) (80:20, v/v) . The ions were detected by a triple quadrupole mass spectrometric detector in the positive mode. Quantification was performed using selected reaction monitoring (SRM) of the transitions m/z 240.88-->197.91 and m/z 285.01-->193.02 for ATT and for the IS, respectively. The analysis time for each run was 5.0 min. The calibration curve fitted well over the concentration range of 0.02-5 ng mL(-1), with the regression equation y = 1.1014x + 0.0003631, r = 0.9992. The intra-batch and inter-batch R.S.D.% were less than 15% at all concentration levels within the calibration range. The recoveries were more than 80%. The present method provides a modern, rapid and robust procedure for the pharmacokinetic study of ATT. Some important pharmacokinetic parameters of ATT in healthy Chinese volunteers are also given for the first time.
Topics: Adult; Anethole Trithione; Chromatography, High Pressure Liquid; Humans; Male; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
PubMed: 17586125
DOI: 10.1016/j.aca.2007.05.038 -
The American Journal of the Medical... Sep 1999Saliva protects the oral mucosa, inhibiting microbial overgrowth. Hyposalivation, therefore, induces multiple oral disorders, although treatment of hyposalivation is... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Saliva protects the oral mucosa, inhibiting microbial overgrowth. Hyposalivation, therefore, induces multiple oral disorders, although treatment of hyposalivation is very difficult.
METHODS
A cholagogue, anethole trithione (AT) was administered to patients with symptomatic hyposalivation (xerostomia) caused by senile hypofunction (4 men and 17 women; senile group), medications (6 men and 17 women; drug group), and oral cancer therapy (two men and three women; cancer group). For control groups, an artificial saliva was administered to 45 patients consisting of senile hypofunction (10 men and 16 women), drug-induced xerostomia (3 men and 10 women) and oral cancer therapy-induced xerostomia (four men and two women).
RESULTS
Two weeks after administration of AT (6 tablets per day), both nonstimulated salivary flow rate (SFR) and stimulated SFR increased in a statistically significantly manner from 0.76 +/- 0.41 and 5.18 +/- 3.02 to 1.54 +/- 1.33 (P<0.05) and 9.07 +/- 4.10 mL/10 min (P<0.05), respectively. Of the three groups, the drug group showed the largest increases in both SFRs, from 0.90 +/- 0.54 and 6.29 +/- 4.12 to 1.69 +/- 1.65 and 12.09 +/- 5.10 mL/10 min (P<0.05 and P<0.02, respectively). Patients in the control group had almost constant SFRs. After AT administration, the salivary viscosity was, however, mildly decreased and concentrations of secretory-immunoglobulin A, lactoferrin, potassium, and chloride in nonstimulated saliva were almost constant. Corresponding with the increase of salivation, oral discomfort and inflammation were improved or resolved in 41 patients of the AT group within about 4 weeks, whereas improvement was observed in only nine patients of the control group.
CONCLUSIONS
These results indicate that AT sufficiently stimulates salivation and improves xerostomia.
Topics: Adult; Aged; Aged, 80 and over; Anethole Trithione; Cholagogues and Choleretics; Female; Humans; Male; Middle Aged; Saliva; Saliva, Artificial; Salivation; Treatment Outcome; Viscosity; Xerostomia
PubMed: 10487404
DOI: 10.1097/00000441-199909000-00009 -
Archives of Toxicology. Supplement. =... 1989
Topics: Acetaminophen; Alanine Transaminase; Anethole Trithione; Animals; Anisoles; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Female; Glutathione; Liver; Mice
PubMed: 2774955
DOI: 10.1007/978-3-642-74117-3_61 -
Cancer Research Aug 1993It has been reported that several naturally occurring and related synthetic organosulfur compounds exert chemopreventive effects in several target organs in rodent...
It has been reported that several naturally occurring and related synthetic organosulfur compounds exert chemopreventive effects in several target organs in rodent models. The chemopreventive actions of 40 and 80% maximum tolerated doses (MTD) of organosulfur compounds, namely anethole trithione, diallyl disulfide, N-acetylcysteine, and taurine, administered in AIN-76A diet, on azoxymethane (AOM)-induced neoplasia were investigated in male F344 rats. Also, the effects of these agents on the activities of phase II enzymes, namely glutathione S-transferase (GST), NAD(P)H-dependent quinone reductase, and UDP-glucuronosyl transferase, in the liver and colonic mucosa and tumors were assessed. The MTD levels of anethole trithione, diallyl disulfide, N-acetylcysteine, and taurine were determined in male F344 rats and found to be 250, 250, 1500, and 1500 ppm, respectively. At 5 weeks of age, animals were fed the control diet (AIN-76A) or experimental diets containing 40 or 80% MTD levels of each test agent. All animals in each group, except those allotted for vehicle (saline) treatment, were administered AOM s.c. at a dose rate of 15 mg/kg body weight once weekly for 2 weeks. All animals were necropsied during week 52 after the second AOM injection. Colonic mucosal and tumor and liver enzyme activities were measured in animals fed 80% MTD levels of each test agent. Colon tumors were subjected to histopathological evaluation and classified as invasive or noninvasive adenocarcinomas. Colon tumor incidence (percentage of animals with tumors) and tumor multiplicity (tumors/animal) were compared among various dietary groups. The results indicated that administration of 200 ppm (80% MTD) anethole trithione significantly inhibited the incidence and multiplicity of both invasive and noninvasive adenocarcinomas, whereas feeding of 100 ppm (40% MTD) anethole trithione or 100 (40% MTD) or 200 ppm (80% MTD) diallyl disulfide suppressed only invasive adenocarcinomas of the colon. Although diets containing N-acetylcysteine and taurine inhibited colon tumor multiplicity, the effect was somewhat marginal. GST, NAD-(P)H-dependent quinone reductase, and UDP-glucuronosyl transferase activities in colonic mucosa and tumor and liver were significantly elevated in animals fed anethole trithione or diallyl disulfide, compared to those fed the control diet. N-Acetylcysteine and taurine slightly but significantly increased only the GST activity in the liver. Although other mechanisms are not excluded, inhibition of AOM-induced colon carcinogenesis by anethole trithione and diallyl disulfide may be associated, in part, with increased activities of phase II enzymes such as GST, NAD(P)H-dependent quinone reductase, and UDP-glucuronosyl transferase in the liver and colon.
Topics: Acetylcysteine; Allyl Compounds; Anethole Trithione; Animals; Anticarcinogenic Agents; Azoxymethane; Colonic Neoplasms; Disulfides; Glucuronosyltransferase; Glutathione Transferase; Male; NAD(P)H Dehydrogenase (Quinone); Rats; Rats, Inbred F344; Taurine
PubMed: 8339252
DOI: No ID Found -
Journal of Pharmaceutical Sciences Nov 2011In this study, an examination of the potential effect of lipids on the first-pass metabolism of anethol trithione (ATT) was investigated. ATT is metabolized rapidly and...
In this study, an examination of the potential effect of lipids on the first-pass metabolism of anethol trithione (ATT) was investigated. ATT is metabolized rapidly and extensively in liver into 4-hydroxy-anethole trithione (ATX), which was confirmed using the rat intestinal perfusion with the mesenteric cannulation model. Male Sprague-Dawley rats were orally administered of the lipid-based formulations (prepared by medium chain triglycerides (MCT)), the cyclodextrin formulation and the suspension formulation, respectively. For 6.75 mg/kg groups, ATX/ATT area under the plasma concentration-time curve (AUC) ratio decreased by 87% and 76% after administration of the MCT-based formulations and the cyclodextrin formulation, when compared with the suspension formulation (p < 0.05), respectively; for 2.25 mg/kg groups, it decreased by 53% in the MCT group when compared with the cyclodextrin group (p < 0.05). The saturation of pre-system metabolism of ATT was observed after administration of the MCT-based formulations and the cyclodextrin formulation, likely as a result of enhanced absorption and therefore presentation of higher drug concentrations to liver, when compared with the suspension formulation. A trend toward lower systemic metabolite to parent ratios was evident after administration of the lipid formulations, when compared with the cyclodextrin formulation; however, this was not statistically significant. Further studies on the potential for lipids to inhibit hepatic metabolism are therefore warranted.
Topics: Anethole Trithione; Animals; Area Under Curve; Intestinal Mucosa; Lipid Metabolism; Male; Models, Biological; Rats; Rats, Sprague-Dawley
PubMed: 21766311
DOI: 10.1002/jps.22702 -
[Zhonghua Yan Ke Za Zhi] Chinese... Jun 2009To investigate anethol trithione therapic efficiency on dry eye. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To investigate anethol trithione therapic efficiency on dry eye.
METHODS
It was a prospective random double-blind controlled study. Eighty cases diagnosed dry eye in Ocular Surface Out-patient Clinic of Xiamen University Affiliated Xiamen Eye Center from 2006 to 2008 were divided into two groups: anethol trithione group and control group, 40 cases in each group. Every group was then divided into two subgroups: weak dry eye subgroup,middle and severe dry eye subgroup. All groups had been added with 0.05% refresh drops. All patients had been detected and evaluated by subjective symptoms of dry eye, visual acuity, corneal fluorescent staining (F1), break-up time (BUT) and Schirmer I test (SIT) at pretherapy and 3, 7, 28 d of post-therapy. All groups had been compared and analyzed by F test and sample mean difference (SMD) or median difference (MD) comparison between pre-therapy and post-therapy.
RESULTS
Except of tear and red eye,the other subjective symptoms of dry eye, Fl, BUT and SIT of weak dry eye subgroup of both groups had been improved at 7 d after therapy. Only those of middle and severe dry eye subgroup of anethol trithione group had been improved at 7 d after therapy compared with those of pretherapy: SMD = 0.96 (visual tiredness), 1.26 (dry and unsmooth sensation), 0.82 (foreign body sensation), 1.28 (burning sensation), 1.05 ( photophobia), 1.48 (pain); MD = 0.30 (visual acuity), 4.00 (Fl), 5.00 (BUT), 5.00 (SIT) [F = 15.30 (visual tiredness), 15.68 (dry and unsmooth sensation), 13.56 (foreign body sensation), 20.91 (burning sensation), 18.90 (photophobia), 27.22 (pain), 10.54 (visual acuity),188.21 (F1), 261.76 (BUT), 269.05 (SIT); P < 0.05]. Those of middle and severe dry eye subgroup of control group hadn't significantly been improved at 28 d after therapy: SMD = 0.10 (visual tiredness), 0.16 (dry and unsmooth sensation), 0.09 (foreign body sensation), 0.38 (burning sensation), 0.24 (photophobia), 0.36 (pain), 0.23 (red eye); MD = 0.10 (visual acuity), 0.50 (Fl), 0.50 (BUT), 0.50 (SIT) [F = 1.76 (visual tiredness), 1.61 (dry and unsmooth sensation), 1.02 (foreign body sensation), 2.39 (burning sensation), 2.42 (photophobia), 2.73 (pain), 2.55 (red eye), 1.46 (visual acuity), 2.35 (Fl), 2.90 (BUT), 2.76 (SIT); P > 0.05]. SIT of anethol trithione group had been improved more significantly after therapy (F = 13.77, P < 0.05).
CONCLUSION
Anethol trithione could significantly improve middle and severe dry eye patients' symptoms and signs whose lacrimal gland function survival and it has clinical application value.
Topics: Adult; Anethole Trithione; Double-Blind Method; Female; Humans; Male; Middle Aged; Prospective Studies; Treatment Outcome; Xerophthalmia
PubMed: 19957670
DOI: No ID Found -
Preventive Medicine 1996Large bowel cancer is one of the leading causes of cancer deaths in the United States and other Western countries. Based on epidemiologic and mechanistic studies,... (Review)
Review
Large bowel cancer is one of the leading causes of cancer deaths in the United States and other Western countries. Based on epidemiologic and mechanistic studies, preclinical studies were designed to evaluate the chemopreventive efficacy of several nonsteroidal antiinflammatory drugs (NSAIDs) and phytochemicals and their synthetic analogues in colon carcinogenesis. These studies demonstrated that NSAIDs such as piroxicam, ibuprofen, aspirin and sulindac, D,L-alpha-difluoromethylornithine, oltipraz, anethole trithione, and diallyl disulfide inhibited colon adenocarcinomas. These results provide compelling rationale to pursue clinical trials in humans.
Topics: Adenocarcinoma; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticarcinogenic Agents; Cell Transformation, Neoplastic; Colonic Neoplasms; Feeding Behavior; Food Additives; Humans; Nutritive Value; Vegetables
PubMed: 8778764
DOI: 10.1006/pmed.1996.0017 -
Macromolecular Bioscience Nov 2015Prodrug micelles carrying 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), a compound possessing chemopreventive properties, are prepared from amphiphilic block...
Prodrug micelles carrying 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), a compound possessing chemopreventive properties, are prepared from amphiphilic block copolymers linking ADT-OH via an ester bond using glycine (PAM-PGlyADT) and isoleucine linkers (PAM-PIleADT). The release of ADT-OH from the PAM-PIleADT micelles is much slower than the PAM-PGlyADT micelles. The PAM-PGlyADT micelles show comparable toxicity with ADT-OH in different cancer cell lines, whereas the PAM-PIleADT micelles are not toxic up to 400 µM. This ADT-ester prodrug micelle approach enables to modulate the release rate of ADT-OH and thus might find application in cancer therapy and prevention.
Topics: Anethole Trithione; Antineoplastic Agents; Humans; Hydrolysis; Micelles; Neoplasms; Prodrugs
PubMed: 26102371
DOI: 10.1002/mabi.201500156