Phenotypical expression of CYP2D6 in Amerindians of Tepehuano origin from Durango, Mexico

Ismael Lares-Asseff, Martha Sosa-Macías, Guillermo Elizondo-Azuela, Carmen Flores-Pérez, Janett Flores-Pérez, Francisco Bradley-Alvarez

Research output: Contribution to conferencePaper

7 Citations (Scopus)

Abstract

Cytochrome P4502D6 (CYP2D6) shows genetic polymorphism, which is clinically important in the metabolism of drugs and other xenobiotics. Dextrometorphan (DM) has been used as a test compound to evaluate the in vivo activity of CYP2D6. Phenotypical frequencies of CYP2D6 have been determined in some populations, but little is known about them in native populations. The object of this study was to characterize the phenotypical expression of CYP2D6 in Amerindian subjects of Tepehuano origin from the State of Durango, using DM as metabolic marker, as well as the effect of age, sex and nutritional status on this activity. Three hr after oral administration of a single 30 mg dose of DM, the plasma concentration of DM and its metabolite dextrophan (DX) were determined with HPLC in 55 Tepehuano subjects. All subjects were extensive metabolizers (metabolic ratio MR <0.3). No correlation of age, sex or nutritional status was found with the DM/DX metabolic ratio. However, we found a monoexponential relationship between the metabolic ratio of DM and DX, and their concentrations respectively, which can have clinical applications, since metabolic ratio can be predicted from a known DM or DX concentration. Three hr after ingestion of DM, 18 individuals showed DM plasma concentrations of 5 to 10 ng/mL, 15 subjects of 11 to 20 ng/mL, 8 subjects of 21 to 50 ng/mL and 14 subjects > 51 ng/mL pointing out that DM concentrations and MR must be determined to establish toxicity risk levels.
Original languageAmerican English
Pages102-107
Number of pages91
StatePublished - 1 Dec 2005
EventProceedings of the Western Pharmacology Society -
Duration: 1 Dec 2005 → …

Conference

ConferenceProceedings of the Western Pharmacology Society
Period1/12/05 → …

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cytochromes
Mexico
metabolites
polymorphism
metabolism
toxicity
markers
drugs
dosage

Cite this

Lares-Asseff, I., Sosa-Macías, M., Elizondo-Azuela, G., Flores-Pérez, C., Flores-Pérez, J., & Bradley-Alvarez, F. (2005). Phenotypical expression of CYP2D6 in Amerindians of Tepehuano origin from Durango, Mexico. 102-107. Paper presented at Proceedings of the Western Pharmacology Society, .
Lares-Asseff, Ismael ; Sosa-Macías, Martha ; Elizondo-Azuela, Guillermo ; Flores-Pérez, Carmen ; Flores-Pérez, Janett ; Bradley-Alvarez, Francisco. / Phenotypical expression of CYP2D6 in Amerindians of Tepehuano origin from Durango, Mexico. Paper presented at Proceedings of the Western Pharmacology Society, .91 p.
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abstract = "Cytochrome P4502D6 (CYP2D6) shows genetic polymorphism, which is clinically important in the metabolism of drugs and other xenobiotics. Dextrometorphan (DM) has been used as a test compound to evaluate the in vivo activity of CYP2D6. Phenotypical frequencies of CYP2D6 have been determined in some populations, but little is known about them in native populations. The object of this study was to characterize the phenotypical expression of CYP2D6 in Amerindian subjects of Tepehuano origin from the State of Durango, using DM as metabolic marker, as well as the effect of age, sex and nutritional status on this activity. Three hr after oral administration of a single 30 mg dose of DM, the plasma concentration of DM and its metabolite dextrophan (DX) were determined with HPLC in 55 Tepehuano subjects. All subjects were extensive metabolizers (metabolic ratio MR <0.3). No correlation of age, sex or nutritional status was found with the DM/DX metabolic ratio. However, we found a monoexponential relationship between the metabolic ratio of DM and DX, and their concentrations respectively, which can have clinical applications, since metabolic ratio can be predicted from a known DM or DX concentration. Three hr after ingestion of DM, 18 individuals showed DM plasma concentrations of 5 to 10 ng/mL, 15 subjects of 11 to 20 ng/mL, 8 subjects of 21 to 50 ng/mL and 14 subjects > 51 ng/mL pointing out that DM concentrations and MR must be determined to establish toxicity risk levels.",
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Lares-Asseff, I, Sosa-Macías, M, Elizondo-Azuela, G, Flores-Pérez, C, Flores-Pérez, J & Bradley-Alvarez, F 2005, 'Phenotypical expression of CYP2D6 in Amerindians of Tepehuano origin from Durango, Mexico', Paper presented at Proceedings of the Western Pharmacology Society, 1/12/05 pp. 102-107.

Phenotypical expression of CYP2D6 in Amerindians of Tepehuano origin from Durango, Mexico. / Lares-Asseff, Ismael; Sosa-Macías, Martha; Elizondo-Azuela, Guillermo; Flores-Pérez, Carmen; Flores-Pérez, Janett; Bradley-Alvarez, Francisco.

2005. 102-107 Paper presented at Proceedings of the Western Pharmacology Society, .

Research output: Contribution to conferencePaper

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AU - Lares-Asseff, Ismael

AU - Sosa-Macías, Martha

AU - Elizondo-Azuela, Guillermo

AU - Flores-Pérez, Carmen

AU - Flores-Pérez, Janett

AU - Bradley-Alvarez, Francisco

PY - 2005/12/1

Y1 - 2005/12/1

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Lares-Asseff I, Sosa-Macías M, Elizondo-Azuela G, Flores-Pérez C, Flores-Pérez J, Bradley-Alvarez F. Phenotypical expression of CYP2D6 in Amerindians of Tepehuano origin from Durango, Mexico. 2005. Paper presented at Proceedings of the Western Pharmacology Society, .