CYP2C19

CYP2C19 metabolizes many compounds including (S)-mephenytoin, omeprazole,
imipramine diazepam, and proguanil. CYP2C19 is detected in the liver and duodenum.

Enzymatic Dehydrogenation

CYP2C19 has been shown to dehydrogenate indapamide into dehydroindapamide. The primary enzyme reponsible for this action was however CYP3A4. CYP2D6 and CYP2A6 also performed this action.[2]

Indapamide	CYP2C19	Dehydroindapamide
	—->

CYP2C19 was able to dehydrogenate estradiol at the 17beta-hydroxy position creating estrone, an action also carried out by CYP2C9 and CYP2C8.[4]

The enzyme Estradiol 17beta-dehydrogenase can also perform this action on estradiol.

Estradiol	CYP2C19	Estrone
	—->

Enzymatic Hydroxylation

CYP2C19 converts estrone into 16alpha-hydroxyestrone.[5]

Estrone	CYP2C19	16alpha-Hydroxyestrone
	—->

---

Inhibitors and Inducers

Potent Inhibitors	Strength	Dosage	Verified in Man
Capsaicin	?	?	?
Curcumin	?	?	?
Nootkatone	?	?	?
Resveratrol	50% Inhibition	IC50=11.6 µM[7]	?
Saint John’s Wort [1]	75% inhibition	High doses	?
Turmeric (contains curcumin)	?	?	?
Inhibitors (unknown potency)	Strength	Dosage	Verified in Man
Bergamottin	?	?	?
Carvone	?	?	?
Dimethylsulfoxide (DMSO)	?	?	?
Feverfew	?	?	?
Glycyrrhizin	?	?	?
Kava	?	?	?
Licorice	?	?	?
Peppermint EO	?	?	?
Pomegranate juice	?	?	?
In Vitro Inhibitors Ineffective in Man	Strength	Dosage	Verified in Man
White Grapefruit [3]	No Inhibition	300 ml	Yes
Ginkgo biloba extract [1]	No Inhibition[6]	120 mg	Yes
Inducers	Strength	Dosage	Verified in Man
Aspirin [8]	"significantly induced"	50 mg daily	Yes
DHEA (dehydroepiandrosterone)	?	?	?
Ginkgo biloba [1]	75% Induction	Low doses	?
Sage [1]	100% Induction	?	?
Saint John’s Wort [1]	134% Induction	Low doses	Yes
Valerian Root [1]	57% Induction	?	?

Bibliography

1. Trade herbal products and induction of CYP2C19 and CYP2E1 in cultured human hepatocytes;

Basic Clin Pharmacol Toxicol. 2009 Jul;105(1):58-63. doi: 10.1111/j.1742-7843.2009.00412.x. Epub 2009 Apr 3; Hellum BH, Hu Z, Nilsen OG; Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway; PubMed PMID: 19371257 (Download Attached PDF Document)

2. Dehydrogenation of the Indoline-Containing Drug 4-Chloro-N-(2-methyl-1-indolinyl)-3-sulfamoylbenzamide (Indapamide) by CYP3A4: Correlation with in Silico Predictions

Hao Sun, Chad Moore, Patrick M. Dansette, Santosh Kumar, James R. Halpert, and Garold S. Yost; PubChem PMCID: PMC2645476

3. Formation of omeprazole sulphone but not 5-hydroxyomeprazole is inhibited by grapefruit juice

Wichittra Tassaneeyakul, Wongwiwat Tassaneeyakul, Suda Vannaprasaht, and Yasushi Yamazoe; 2000; PubChem PMCID: PMC2014902

4. Role of cytochrome P450 in estradiol metabolism in vitro.

Cheng ZN, Shu Y, Liu ZQ, Wang LS, Ou-Yang DS, Zhou HH. PubMed PMID: 11741520 (Download Attached PDF Document)

5. Role of polymorphic human cytochrome P450 enzymes in estrone oxidation.

Cribb AE, Knight MJ, Dryer D, Guernsey J, Hender K, Tesch M, Saleh TM. PubMed PMID: 16537715

6. Effects of Ginkgo biloba extracts on diazepam metabolism: a pharmacokinetic study in healthy Chinese male subjects.

Zuo XC, Zhang BK, Jia SJ, Liu SK, Zhou LY, Li J, Zhang J, Dai LL, Chen BM, Yang GP, Yuan H. PubMed PMID: 20186406

7. Liquid chromatography/tandem mass spectrometric determination of inhibition of human cytochrome P450 isozymes by resveratrol and resveratrol-3-sulfate.

Yu C, Shin YG, Kosmeder JW, Pezzuto JM, van Breemen RB. PubMed PMID: 12569440

8. Isozyme-specific induction of low-dose aspirin on cytochrome P450 in healthy subjects'

Chen XP1, Tan ZR, Huang SL, Huang Z, Ou-Yang DS, Zhou HH.; Clin Pharmacol Ther. 2003 Mar;73(3):264-71; PMID: 12621391