Pharmacogenetics of amfepramone in healthy Mexican subjects reveals potential markers for tailoring pharmacotherapy of obesity: results of a randomised trial

Magdalena Gómez-Silva, Everardo Piñeyro-Garza, Rigoberto Vargas-Zapata, María E. Gamino-Peña, Mario Bermúdez de León, Adrián Llerena, Armando León-García, Rafael B R Leon-Cachon

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number17833
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

Fingerprint

Diethylpropion
Pharmacogenetics
Healthy Volunteers
Obesity
Drug Therapy
Cytochrome P-450 CYP3A
Pharmacokinetics
Phenotype
Linear Models
Population
Appetite Depressants
Genetic Markers
Genes
Real-Time Polymerase Chain Reaction
Mass Spectrometry
High Pressure Liquid Chromatography

All Science Journal Classification (ASJC) codes

  • General

Cite this

Gómez-Silva, Magdalena ; Piñeyro-Garza, Everardo ; Vargas-Zapata, Rigoberto ; Gamino-Peña, María E. ; Bermúdez de León, Mario ; Llerena, Adrián ; León-García, Armando ; Leon-Cachon, Rafael B R. / Pharmacogenetics of amfepramone in healthy Mexican subjects reveals potential markers for tailoring pharmacotherapy of obesity: results of a randomised trial. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
@article{9620fae4f9644f52b591f8be3970a3a8,
title = "Pharmacogenetics of amfepramone in healthy Mexican subjects reveals potential markers for tailoring pharmacotherapy of obesity: results of a randomised trial",
abstract = "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.",
author = "Magdalena G{\'o}mez-Silva and Everardo Pi{\~n}eyro-Garza and Rigoberto Vargas-Zapata and Gamino-Pe{\~n}a, {Mar{\'i}a E.} and {Berm{\'u}dez de Le{\'o}n}, Mario and Adri{\'a}n Llerena and Armando Le{\'o}n-Garc{\'i}a and Leon-Cachon, {Rafael B R}",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41598-019-54436-z",
language = "English",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

Pharmacogenetics of amfepramone in healthy Mexican subjects reveals potential markers for tailoring pharmacotherapy of obesity: results of a randomised trial. / Gómez-Silva, Magdalena; Piñeyro-Garza, Everardo; Vargas-Zapata, Rigoberto; Gamino-Peña, María E.; Bermúdez de León, Mario; Llerena, Adrián; León-García, Armando; Leon-Cachon, Rafael B R.

In: Scientific Reports, Vol. 9, No. 1, 17833, 01.12.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pharmacogenetics of amfepramone in healthy Mexican subjects reveals potential markers for tailoring pharmacotherapy of obesity: results of a randomised trial

AU - Gómez-Silva, Magdalena

AU - Piñeyro-Garza, Everardo

AU - Vargas-Zapata, Rigoberto

AU - Gamino-Peña, María E.

AU - Bermúdez de León, Mario

AU - Llerena, Adrián

AU - León-García, Armando

AU - Leon-Cachon, Rafael B R

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85075737792&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85075737792&partnerID=8YFLogxK

U2 - 10.1038/s41598-019-54436-z

DO - 10.1038/s41598-019-54436-z

M3 - Article

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 17833

ER -