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Statements

Subject Item
n2:RIV%2F60077395%3A_____%2F03%3A60033099%21RIV%2F2004%2FAV0%2FA60004%2FN
rdf:type
n9:Vysledek skos:Concept
dcterms:description
Paclitaxel is an important, recently introduced anti-neoplastic drug. Paclitaxel metabolites are virtually inactive in comparison with the parent drug. The study investigated whether phenolic antioxidants could inhibit metabolic inactivation sufficiently to increase paclitaxel effects. Cytochrome P450 (CYP)-catalysed metabolism of paclitaxel was investigated in rat and human liver microsomes. In rat microsomes, paclitaxel was metabolised mainly to C3'-hydroxypaclitaxel (C3'-OHP), less to C2-hydroxypaclitaxel (C2-OHP), di-hydroxypaclitaxel (di-OHP) and another monohydroxylated paclitaxel. In human liver microsomes, 6alpha-hydroxypaclitaxel (6alpha-OHP), formed by CYP2C8, was the main metabolite, while C3'-OHP, C2-OHP and another product different from di-OHP were minor metabolites, formed by CYP3A4. In individual human livers 6alpha-OHP was formed at 1.8-fold to 13-fold higher rates than C3'-OHP. Kinetic parameters (K-m and V-max) of production of various metabolites in rat and human liver microsomes r Paclitaxel is an important, recently introduced anti-neoplastic drug. Paclitaxel metabolites are virtually inactive in comparison with the parent drug. The study investigated whether phenolic antioxidants could inhibit metabolic inactivation sufficiently to increase paclitaxel effects. Cytochrome P450 (CYP)-catalysed metabolism of paclitaxel was investigated in rat and human liver microsomes. In rat microsomes, paclitaxel was metabolised mainly to C3'-hydroxypaclitaxel (C3'-OHP), less to C2-hydroxypaclitaxel (C2-OHP), di-hydroxypaclitaxel (di-OHP) and another monohydroxylated paclitaxel. In human liver microsomes, 6alpha-hydroxypaclitaxel (6alpha-OHP), formed by CYP2C8, was the main metabolite, while C3'-OHP, C2-OHP and another product different from di-OHP were minor metabolites, formed by CYP3A4. In individual human livers 6alpha-OHP was formed at 1.8-fold to 13-fold higher rates than C3'-OHP. Kinetic parameters (K-m and V-max) of production of various metabolites in rat and human liver microsomes r
dcterms:title
Paclitaxel metabolism in rat and human liver microsomes is inhibited by phenolic antioxidants. Paclitaxel metabolism in rat and human liver microsomes is inhibited by phenolic antioxidants.
skos:prefLabel
Paclitaxel metabolism in rat and human liver microsomes is inhibited by phenolic antioxidants. Paclitaxel metabolism in rat and human liver microsomes is inhibited by phenolic antioxidants.
skos:notation
RIV/60077395:_____/03:60033099!RIV/2004/AV0/A60004/N
n3:strany
200;209
n3:aktivita
n14:Z n14:P
n3:aktivity
P(IPP1050128), P(NL6715), P(NL7567), Z(AV0Z5007907), Z(MZ023795.0001)
n3:cisloPeriodika
N/A
n3:dodaniDat
n10:2004
n3:domaciTvurceVysledku
n11:8519064
n3:druhVysledku
n15:J
n3:duvernostUdaju
n12:S
n3:entitaPredkladatele
n6:predkladatel
n3:idSjednocenehoVysledku
620225
n3:idVysledku
RIV/60077395:_____/03:60033099
n3:jazykVysledku
n18:eng
n3:klicovaSlova
paclitaxel; cytochrome P450; rat
n3:klicoveSlovo
n7:cytochrome%20P450 n7:rat n7:paclitaxel
n3:kodStatuVydavatele
US - Spojené státy americké
n3:kontrolniKodProRIV
[1CDD2D1AE222]
n3:nazevZdroje
Naunyn-Schmiedebergs Archives of Pharmacology
n3:obor
n13:FR
n3:pocetDomacichTvurcuVysledku
1
n3:pocetTvurcuVysledku
4
n3:pocetUcastnikuAkce
0
n3:pocetZahranicnichUcastnikuAkce
0
n3:projekt
n16:IPP1050128 n16:NL6715 n16:NL7567
n3:rokUplatneniVysledku
n10:2003
n3:svazekPeriodika
368
n3:tvurceVysledku
Gut, I. Václavíková, R. Šimek, Petr Horský, S.
n3:zamer
n8:AV0Z5007907 n8:MZ023795.0001
s:issn
0028-1298
s:numberOfPages
10