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Dear PK Group members,
Has any one in the group seen differences in metabolism (via phase 2)
between Japanese and Caucasian subjects.
Any reference(s) will be helpful.
Thank you in advance.
Raju
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The following message was posted to: PharmPK
Dear Raju
As part of my dissertation, I'd looked at the excretion of aspirin
metabolites in Caucasian and Asian subjects (of Vietnamese origin)
amongst, other groups. I found that the excretion of salicylacyl
glucuronide was significantly lower and excretion of salicyluric acid
significantly higher in the Caucasian subjects compared to the Asian
subjects. Let me know if you'd like more information.
Regards
Suresh
Suresh Mallikaarjun, PhD, FCP
2440 Research Boulevard
Rockville, MD 20850
Ph: 240-683-3221
e-mail: suresh.mallikaarjun.-a-.otsuka.com
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Hi Raju,
You may want to specify which phase 2 enzyme you are looking for.
There are several gentetic polymorphisms observed in Phase 2 drug
metabolism enzymes like UGT, Sulfation, Acetylation, Nacetylation,
GST and methylation.
Some PubMed references...
1. Bhasker CR et al . Pharmacogenetics. Genetic polymorphism of UDP-
glucuronosyltransferase 2B7 (UGT2B7) at amino acid 268: ethnic
diversity of alleles and potential clinical significance. 2000 Nov;10
(8):679-85.
2. Saito Ket al . Haplotype analysis of UDP-glucuronocyltransferase
2B7 gene (UGT2B7) polymorphisms in healthy Japanese subjects. Clin
Biochem. 2006 Mar;39(3):303-8. Epub 2006 Feb 8.
3. Hiratsuka M et al. Genetic analysis of thiopurine
methyltransferase polymorphism in a Japanese population. Mutat Res.
2000 Mar 14;448(1):91-5
4. Ozawa Set al . Sulfating-activity and stability of cDNA-expressed
allozymes of human phenol sulfotransferase, ST1A3*1 ((213)Arg) and
ST1A3*2 ((213)His), both of which exist in Japanese as well as
Caucasians. J Biochem (Tokyo). 1999 Aug;126(2):271-7.
Cheers
Ganesh
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Ethnic differences in the metabolism of drugs undergoing N-
glucuronidation should be studied. Ethnic differences have also been
reported for hydroxyglucuronide formation of codeine between Chinese
and whites of Swedish background (Yue et al., 1989).
Interestingly, drugs metabolized by CYP2D6 will not exhibit racial
differences in their disposition.
Listed below please find some references:
1. Ethnic differences in N-glucuronidation of nicotine and cotinine.
2. Journal of pharmacology and experimental therapeutics, Vol.
291, Issue 3, 1196-1203, December 1999.
3. Metoprolol metabolism via cytochromeP4502D6 ethnic
populations, Drug Metab. Dispos. 1996, 24:350-355.
Regards,
Anila
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There is evidence out there. Here are a few references:
1: Sun D, Chen G, Dellinger RW, Duncan K, Fang JL, Lazarus P.
Characterization of tamoxifen and 4-hydroxytamoxifen glucuronidation
by human
UGT1A4 variants.
Breast Cancer Res. 2006 Aug 2;8(4):R50 [Epub ahead of print]
PMID: 16884532 [PubMed - as supplied by publisher]
2: Nagar S, Blanchard RL.
Pharmacogenetics of uridine diphosphoglucuronosyltransferase (UGT) 1A
family
members and its role in patient response to irinotecan.
Drug Metab Rev. 2006;38(3):393-409. Review.
PMID: 16877259 [PubMed - indexed for MEDLINE]
3: Takekuma Y, Takenaka T, Kiyokawa M, Yamazaki K, Okamoto H,
Kitabatake A,
Tsutsui H, Sugawara M.
Contribution of polymorphisms in UDP-glucuronosyltransferase and
CYP2D6 to the
individual variation in disposition of carvedilol.
J Pharm Pharm Sci. 2006;9(1):101-12.
PMID: 16849011 [PubMed - indexed for MEDLINE]
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