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Titolo:
EVALUATION OF OMEPRAZOLE AND LANSOPRAZOLE AS INHIBITORS OF CYTOCHROME-P450 ISOFORMS
Autore:
KO JW; SUKHOVA N; THACKER D; CHEN P; FLOCKHART DA;
Indirizzi:
GEORGETOWN UNIV,MED CTR,DIV CLIN PHARMACOL,DEPT MED,3900 RESERVOIR RDNW WASHINGTON DC 20007 GEORGETOWN UNIV,MED CTR,DEPT PHARMACOL WASHINGTON DC 20007
Titolo Testata:
Drug metabolism and disposition
fascicolo: 7, volume: 25, anno: 1997,
pagine: 853 - 862
SICI:
0090-9556(1997)25:7<853:EOOALA>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-LIVER-MICROSOMES; S-MEPHENYTOIN 4'-HYDROXYLATION; OXIDATIVE DRUG-METABOLISM; STEADY-STATE; SELECTIVE INHIBITORS; PLASMA-LEVELS; DIAZEPAM; HYDROXYLATION; CYP2D6; DEXTROMETHORPHAN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
65
Recensione:
Indirizzi per estratti:
Citazione:
J.W. Ko et al., "EVALUATION OF OMEPRAZOLE AND LANSOPRAZOLE AS INHIBITORS OF CYTOCHROME-P450 ISOFORMS", Drug metabolism and disposition, 25(7), 1997, pp. 853-862

Abstract

The human clearance of omeprazole and lansoprazole is conducted primarily by the hepatic cytochrome P450 (CYP) system. Efficacy data indicate few differences between these two drugs, but they may exhibit discrete drug interaction profiles. To compare the potency and specificity of these drugs as inhibitors of CYP isoforms, we performed in vitro studies with human liver microsomal preparations. Both drugs were potent, competitive inhibitors of CYP2C19, as measured by the conversion of S-mephenytoin to 4-hydroxymephenytoin (k(i) = 3.1 +/- 2.2 mu M for omeprazole, K-i = 3.2 +/- 1.3 mu M for lansoprazole). For omeprazole, thehighest concentration at which >70% inhibition of CYP2C19 was observed with no significant inhibitory effect on other isoforms was at least20 times greater than K-i. Both drugs were competitive inhibitors of CYP2C9-catalyzed conversion of tolbutamide to 4-hydroxytolbutamide (K-i = 40.1 +/- 14.8 mu M for omeprazole, K-i = 52.1 +/- 1.4 mu M for lansoprazole) and were noncompetitive inhibitors of CYP3A-catalyzed conversion of dextromethorphan to 3-methoxymorphinan (K-i = 84.4 +/- 4.0 muM for omeprazole, K-i = 170.4 +/- 7.1 mu M for lansoprozole). Lansoprazole was at least 5 times more potent (K-i = 44.7 +/- 22.0 mu M) thanomeprazole (k(i) = 240.7 +/- 102.0 mu M) as an inhibitor of CYP2D6-mediated conversion of dextromethorphan to dextrorphan. No inhibition ofCYP1A2, assessed by measuring the conversion of phenacetin to acetaminophen, was noted. Our data suggest that whereas the inhibitory profiles of these two drugs are similar, lansoprazole may be the more important in vitro inhibitor of CYP2D6. Since its inhibition is very potent and has a broad ''window of selectivity,'' omeprazole seems to be a useful, selective inhibitor of CYP2C19.

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Documento generato il 23/01/20 alle ore 03:37:49