Effects of repeated green tea catechin administration on human cytochrome P450 activity

Hsiao-Hui Chow, Iman A Hakim, Donna R. Vining, James A. Crowell, Catherine A. Cordova, Wade M. Chew, Min Jian Xu, Chiu-Hsieh Hsu, James Ranger-Moore, David S Alberts

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Purpose: Preclinical studies suggested that green tea or green tea catechins can modulate the activities of drug-metabolizing enzymes. We conducted this clinical study to determine the effect of repeated green tea catechin administration on human cytochrome P450 (CYP) enzyme activities. Methods: Forty-two healthy volunteers underwent a 4-week washout period by refraining from tea or tea-related products. At the end of the washout period, study participants received a cocktail of CYP metabolic probe drugs, including caffeine, dextromethorphan, losartan, and buspirone for assessing the activity of CYP1A2, CYP2D6, CYP2C9, and CYP3A4, respectively. Blood and urine samples before and 8 h after probe drug administration were collected to determine parent drug and metabolite concentrations for measurements of baseline CYP enzyme activities. Following the baseline evaluation, study participants underwent 4 weeks of green tea catechin intervention at a dose that contains 800 mg epigallocatechin gallate (EGCG) daily. The green tea catechin product was taken on an empty stomach to optimize the p.o. bioavailability of EGCG. The EGCG dose given in this study exceeded the amounts provided by average green tea consumption. Upon completion of the green tea catechin intervention, the postintervention CYP enzyme activities were evaluated as described above. Results: There are large between-subject variations in CYP enzyme activities in healthy individuals. Four weeks of green tea catechin intervention did not alter the phenotypic indices of CYP1A2, CYP12D6, and CYP12C9, but resulted in a 20% increase (P = 0.01) in the area under the plasma buspirone concentration-time profile, suggesting a small reduction in CYP3A4 activity. Conclusions: We conclude that repeated green tea catechin administration is not likely to result in clinically significant effects on the disposition of drugs metabolized by CYP enzymes.

Original languageEnglish (US)
Pages (from-to)2473-2476
Number of pages4
JournalCancer Epidemiology Biomarkers and Prevention
Volume15
Issue number12
DOIs
StatePublished - Dec 2006

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Catechin
Tea
Cytochrome P-450 Enzyme System
Buspirone
Cytochrome P-450 CYP3A
Cytochrome P-450 CYP1A2
Pharmaceutical Preparations
Dextromethorphan
Cytochrome P-450 CYP2D6
Losartan
Caffeine
Biological Availability
Stomach
Healthy Volunteers
Parents
Urine

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Effects of repeated green tea catechin administration on human cytochrome P450 activity. / Chow, Hsiao-Hui; Hakim, Iman A; Vining, Donna R.; Crowell, James A.; Cordova, Catherine A.; Chew, Wade M.; Xu, Min Jian; Hsu, Chiu-Hsieh; Ranger-Moore, James; Alberts, David S.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 15, No. 12, 12.2006, p. 2473-2476.

Research output: Contribution to journalArticle

Chow, Hsiao-Hui ; Hakim, Iman A ; Vining, Donna R. ; Crowell, James A. ; Cordova, Catherine A. ; Chew, Wade M. ; Xu, Min Jian ; Hsu, Chiu-Hsieh ; Ranger-Moore, James ; Alberts, David S. / Effects of repeated green tea catechin administration on human cytochrome P450 activity. In: Cancer Epidemiology Biomarkers and Prevention. 2006 ; Vol. 15, No. 12. pp. 2473-2476.
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abstract = "Purpose: Preclinical studies suggested that green tea or green tea catechins can modulate the activities of drug-metabolizing enzymes. We conducted this clinical study to determine the effect of repeated green tea catechin administration on human cytochrome P450 (CYP) enzyme activities. Methods: Forty-two healthy volunteers underwent a 4-week washout period by refraining from tea or tea-related products. At the end of the washout period, study participants received a cocktail of CYP metabolic probe drugs, including caffeine, dextromethorphan, losartan, and buspirone for assessing the activity of CYP1A2, CYP2D6, CYP2C9, and CYP3A4, respectively. Blood and urine samples before and 8 h after probe drug administration were collected to determine parent drug and metabolite concentrations for measurements of baseline CYP enzyme activities. Following the baseline evaluation, study participants underwent 4 weeks of green tea catechin intervention at a dose that contains 800 mg epigallocatechin gallate (EGCG) daily. The green tea catechin product was taken on an empty stomach to optimize the p.o. bioavailability of EGCG. The EGCG dose given in this study exceeded the amounts provided by average green tea consumption. Upon completion of the green tea catechin intervention, the postintervention CYP enzyme activities were evaluated as described above. Results: There are large between-subject variations in CYP enzyme activities in healthy individuals. Four weeks of green tea catechin intervention did not alter the phenotypic indices of CYP1A2, CYP12D6, and CYP12C9, but resulted in a 20{\%} increase (P = 0.01) in the area under the plasma buspirone concentration-time profile, suggesting a small reduction in CYP3A4 activity. Conclusions: We conclude that repeated green tea catechin administration is not likely to result in clinically significant effects on the disposition of drugs metabolized by CYP enzymes.",
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T1 - Effects of repeated green tea catechin administration on human cytochrome P450 activity

AU - Chow, Hsiao-Hui

AU - Hakim, Iman A

AU - Vining, Donna R.

AU - Crowell, James A.

AU - Cordova, Catherine A.

AU - Chew, Wade M.

AU - Xu, Min Jian

AU - Hsu, Chiu-Hsieh

AU - Ranger-Moore, James

AU - Alberts, David S

PY - 2006/12

Y1 - 2006/12

N2 - Purpose: Preclinical studies suggested that green tea or green tea catechins can modulate the activities of drug-metabolizing enzymes. We conducted this clinical study to determine the effect of repeated green tea catechin administration on human cytochrome P450 (CYP) enzyme activities. Methods: Forty-two healthy volunteers underwent a 4-week washout period by refraining from tea or tea-related products. At the end of the washout period, study participants received a cocktail of CYP metabolic probe drugs, including caffeine, dextromethorphan, losartan, and buspirone for assessing the activity of CYP1A2, CYP2D6, CYP2C9, and CYP3A4, respectively. Blood and urine samples before and 8 h after probe drug administration were collected to determine parent drug and metabolite concentrations for measurements of baseline CYP enzyme activities. Following the baseline evaluation, study participants underwent 4 weeks of green tea catechin intervention at a dose that contains 800 mg epigallocatechin gallate (EGCG) daily. The green tea catechin product was taken on an empty stomach to optimize the p.o. bioavailability of EGCG. The EGCG dose given in this study exceeded the amounts provided by average green tea consumption. Upon completion of the green tea catechin intervention, the postintervention CYP enzyme activities were evaluated as described above. Results: There are large between-subject variations in CYP enzyme activities in healthy individuals. Four weeks of green tea catechin intervention did not alter the phenotypic indices of CYP1A2, CYP12D6, and CYP12C9, but resulted in a 20% increase (P = 0.01) in the area under the plasma buspirone concentration-time profile, suggesting a small reduction in CYP3A4 activity. Conclusions: We conclude that repeated green tea catechin administration is not likely to result in clinically significant effects on the disposition of drugs metabolized by CYP enzymes.

AB - Purpose: Preclinical studies suggested that green tea or green tea catechins can modulate the activities of drug-metabolizing enzymes. We conducted this clinical study to determine the effect of repeated green tea catechin administration on human cytochrome P450 (CYP) enzyme activities. Methods: Forty-two healthy volunteers underwent a 4-week washout period by refraining from tea or tea-related products. At the end of the washout period, study participants received a cocktail of CYP metabolic probe drugs, including caffeine, dextromethorphan, losartan, and buspirone for assessing the activity of CYP1A2, CYP2D6, CYP2C9, and CYP3A4, respectively. Blood and urine samples before and 8 h after probe drug administration were collected to determine parent drug and metabolite concentrations for measurements of baseline CYP enzyme activities. Following the baseline evaluation, study participants underwent 4 weeks of green tea catechin intervention at a dose that contains 800 mg epigallocatechin gallate (EGCG) daily. The green tea catechin product was taken on an empty stomach to optimize the p.o. bioavailability of EGCG. The EGCG dose given in this study exceeded the amounts provided by average green tea consumption. Upon completion of the green tea catechin intervention, the postintervention CYP enzyme activities were evaluated as described above. Results: There are large between-subject variations in CYP enzyme activities in healthy individuals. Four weeks of green tea catechin intervention did not alter the phenotypic indices of CYP1A2, CYP12D6, and CYP12C9, but resulted in a 20% increase (P = 0.01) in the area under the plasma buspirone concentration-time profile, suggesting a small reduction in CYP3A4 activity. Conclusions: We conclude that repeated green tea catechin administration is not likely to result in clinically significant effects on the disposition of drugs metabolized by CYP enzymes.

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