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How do you use in vitro stability data, t1/2, of a compoundin control
plasma to estimate plasma clearance?
Thanks
Sureb Al-Fast
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Sureb,
Here are some references that might help. The article in DMD, 1999
gives the relevant formula for extrapolating the in vitro t1/2 to in
vivo clearance.
-Saileta
The prediction of human clearance from hepatic microsomal metabolism
data.
Curr Opin Drug Discov Devel. 2001 Jan;4(1):36-44. Review.
PMID: 11727321 [PubMed - indexed for MEDLINE]
2: Obach RS. Related Articles, Links
Prediction of human clearance of twenty-nine drugs from hepatic
microsomal intrinsic clearance data: An examination of in vitro
half-life approach and nonspecific binding to microsomes.
Drug Metab Dispos. 1999 Nov;27(11):1350-9.
PMID: 10534321 [PubMed - indexed for MEDLINE]
3: Obach RS. Related Articles, Links
Nonspecific binding to microsomes: impact on scale-up of in vitro
intrinsic clearance to hepatic clearance as assessed through
examination of warfarin, imipramine, and propranolol.
Drug Metab Dispos. 1997 Dec;25(12):1359-69.
PMID: 9394025 [PubMed - indexed for MEDLINE]
4: Obach RS, Baxter JG, Liston TE, Silber BM, Jones BC, MacIntyre F,
Rance DJ, Wastall P. Related Articles, Links
The prediction of human pharmacokinetic parameters from preclinical and
in vitro metabolism data.
J Pharmacol Exp Ther. 1997 Oct;283(1):46-58.
PMID: 9336307 [PubMed - indexed for MEDLINE]
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Thanks Saileta. But the plasma cannot be treated in the same way as
liver. Would you extrapolate to Vz or Volume of plasma in the body
or...?
Sureb
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