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Drug Testing and Analysis Jan 2022In recent years, overseas anti-obesity drugs including amfepramone have flowed into China through the internet or personal import by travelers. Amfepramone is controlled...
In recent years, overseas anti-obesity drugs including amfepramone have flowed into China through the internet or personal import by travelers. Amfepramone is controlled in China and is not available as a pharmaceutical product. It is obtainable either through the internet or imported by individuals across the border. The abuse of amfepramone is causing serious health problems. A method for the detection and quantification of amfepramone and its metabolite cathinone in human hair was developed and fully validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Approximately 10 mg of hair was weighed and pulverized with extraction solvent (a mixture of methanol: acetonitrile: 2 mM ammonium formate [pH 5.3] [25:29:46, v/v/v]). The limit of detection (LOD) and the limit of quantitation (LOQ) were 5 and 10 pg/mg, respectively. The method was linear over a concentration range from 10 to 10,000 pg/mg. The accuracy varied from -9.3% to 2.3%, with acceptable intra- and inter-day precision. The validated method was successfully applied to 17 authentic cases. The amfepramone concentrations ranged from 11.7 to 209 pg/mg, with a median of 30.2 pg/mg, and the hair cathinone concentrations ranged from 11.9 to 507 pg/mg, with a median of 54.0 pg/mg. This is the first report of amfepramone concentrations in human hair from amfepramone users. Cathinone can be incorporated into hair after amfepramone use.
Topics: Adult; Alkaloids; Appetite Depressants; Chromatography, Liquid; Diethylpropion; Female; Hair; Humans; Limit of Detection; Male; Middle Aged; Substance Abuse Detection; Tandem Mass Spectrometry
PubMed: 34405558
DOI: 10.1002/dta.3149 -
Clinical Therapeutics Mar 2022Nearly 90% of individuals with type 2 diabetes mellitus (T2DM) are either overweight or obese, placing them at high risk of microvascular and macrovascular...
PURPOSE
Nearly 90% of individuals with type 2 diabetes mellitus (T2DM) are either overweight or obese, placing them at high risk of microvascular and macrovascular complications. The main objective of this study was to assess the use of antiobesity medications and antihyperglycemic agents that produce weight gain among patients with T2DM who qualify for National Institutes of Health guideline-recommended pharmacologic weight loss therapy.
METHODS
This study used the 2005-2006 through 2015-2016 biannual cycles of the National Health and Nutrition Examination Survey and included adults aged ≥20 years who reported a diagnosis of T2DM and who qualified for antiobesity treatment (defined as a body mass index ≥27 kg/m) at the time of physical examination. Antiobesity medication use was defined as use of orlistat, phentermine, diethylpropion, lorcaserin, phentermine/topiramate, bupropion/naltrexone, or liraglutide. Use of weight-inducing antihyperglycemic agents was defined as use of sulfonylureas, thiazolidinediones, or insulin (any type), either alone or in combination with any other antihyperglycemic agent regardless of effect on weight.
FINDINGS
Among adults with T2DM who qualified for antiobesity treatment (N = 2910), only 40 participants (2.2%; 95% CI, 1.5-3.3) were on pharmacologic antiobesity treatment within 30 days of survey interview. The only antiobesity medications identified were liraglutide (n = 34 [1.9%]), phentermine (n = 4 [0.2%]), orlistat (n = 1 [0.1%]), and phentermine/topiramate (n = 1 [0.0%]). Among those who were on antihyperglycemic treatment (n = 2401), 1661 (66%; 95% CI, 63.1-68.8) were on weight-inducing antihyperglycemic agents; however, a downward trend in the use of these agents over time was observed (from 78.4% in 2005-2006 to 53.3% in 2015-2016; P < 0.0005).
IMPLICATIONS
This is the first national epidemiologic study evaluating the use of antiobesity medications and weight-inducing antihyperglycemic agents among patients with T2DM who qualify for weight loss therapy. This study documents that patients are not on guideline-directed weight loss therapy. Furthermore, weight loss goals are likely compromised by 66% of individuals being on weight-inducing antihyperglycemic therapy. Use of antiobesity medications could play a significant role in promoting weight loss and potentially lead to a healthier lifestyle, which could reduce microvascular and macrovascular complications. Stronger recommendations in using guideline-directed therapy in obesity complicated by T2DM are necessary.
Topics: Adult; Anti-Obesity Agents; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Liraglutide; Nutrition Surveys; Obesity; Orlistat; Phentermine; Prevalence; Topiramate; United States; Weight Loss
PubMed: 35105470
DOI: 10.1016/j.clinthera.2022.01.003 -
Scientific Reports Nov 2019Amfepramone (AFP) is an appetite-suppressant drug used in the treatment of obesity. Nonetheless, studies on interindividual pharmacokinetic variability and its... (Randomized Controlled Trial)
Randomized Controlled Trial
Amfepramone (AFP) is an appetite-suppressant drug used in the treatment of obesity. Nonetheless, studies on interindividual pharmacokinetic variability and its association with genetic variants are limited. We employed a pharmacokinetic and pharmacogenetic approach to determine possible metabolic phenotypes of AFP and identify genetic markers that could affect the pharmacokinetic variability in a Mexican population. A controlled, randomized, crossover, single-blind, two-treatment, two-period, and two sequence clinical study of AFP (a single 75 mg dose) was conducted in 36 healthy Mexican volunteers who fulfilled the study requirements. Amfepramone plasma levels were measured using high-performance liquid chromatography mass spectrometry. Genotyping was performed using real-time PCR with TaqMan probes. Four AFP metabolizer phenotypes were found in our population: slow, normal, intermediate, and fast. Additionally, two gene polymorphisms, ABCB1-rs1045642 and CYP3A4-rs2242480, had a significant effect on AFP pharmacokinetics (P < 0.05) and were the predictor factors in a log-linear regression model. The ABCB1 and CYP3A4 gene polymorphisms were associated with a fast metabolizer phenotype. These results suggest that metabolism of AFP in the Mexican population is variable. In addition, the genetic variants ABCB1-rs1045642 and CYP3A4-rs2242480 may partially explain the AFP pharmacokinetic variability.
Topics: ATP Binding Cassette Transporter, Subfamily B; Adult; Appetite Depressants; Cytochrome P-450 CYP3A; Diethylpropion; Female; Humans; Male; Metabolic Clearance Rate; Middle Aged; Pharmacogenomic Variants; Polymorphism, Single Nucleotide
PubMed: 31780765
DOI: 10.1038/s41598-019-54436-z