Pharmacogenetics of amfepramone in healthy Mexican subjects reveals potential markers for tailoring pharmacotherapy of obesity: results of a randomised trial.
Magdalena Gómez-SilvaEverardo Piñeyro-GarzaRigoberto Vargas-ZapataMaría Elena Gamino-PeñaArmando León-GarcíaMario Bermúdez de LeónAdrián LlerenaRafael Baltazar Reyes León-CachónPublished in: Scientific reports (2019)
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.
Keyphrases
- high performance liquid chromatography
- mass spectrometry
- real time pcr
- weight loss
- metabolic syndrome
- double blind
- open label
- insulin resistance
- type diabetes
- genome wide
- simultaneous determination
- placebo controlled
- small molecule
- study protocol
- randomized controlled trial
- high resolution
- high throughput
- emergency department
- dna methylation
- combination therapy
- copy number
- human health
- phase ii
- fluorescence imaging
- electronic health record