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Titolo:
Theophylline pharmacokinetics are not altered by lansoprazole in CYP2C19 poor metabolizers
Autore:
Ko, JW; Jang, IJ; Shin, JG; Nam, SK; Shin, SG; Flockhart, DA;
Indirizzi:
Georgetown Univ, Med Ctr, Div Clin Pharmacol, Dept Med, Washington, DC 20007 USA Georgetown Univ Washington DC USA 20007 ept Med, Washington, DC 20007 USA Seoul Natl Univ, Coll Med, Dept Pharmacol, Seoul, South Korea Seoul Natl Univ Seoul South Korea d, Dept Pharmacol, Seoul, South Korea Seoul Natl Univ Hosp, Clin Pharmacol Unit, Seoul 110744, South Korea SeoulNatl Univ Hosp Seoul South Korea 110744 Seoul 110744, South Korea
Titolo Testata:
CLINICAL PHARMACOLOGY & THERAPEUTICS
fascicolo: 6, volume: 65, anno: 1999,
pagine: 606 - 614
SICI:
0009-9236(199906)65:6<606:TPANAB>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACID-RELATED DISORDERS; HUMAN LIVER-MICROSOMES; S-MEPHENYTOIN; CYTOCHROME-P450 ISOFORMS; OMEPRAZOLE METABOLISM; BREATH TEST; HYDROXYLATION; DISPOSITION; INHIBITORS; IDENTIFICATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Flockhart, DA Georgetown Univ, Med Ctr, Div Clin Pharmacol, Dept Med, 3900Reservoir Rd NW, Washington, DC 20007 USA Georgetown Univ 3900 Reservoir Rd NW Washington DC USA 20007
Citazione:
J.W. Ko et al., "Theophylline pharmacokinetics are not altered by lansoprazole in CYP2C19 poor metabolizers", CLIN PHARM, 65(6), 1999, pp. 606-614

Abstract

Lansoprazole is a potent gastric proton pump inhibitor that is metabolizedby CYP2C19 but appears to induce the activity of hepatic microsomal CYP1A2in a concentration-dependent manner. Because the inducing effect appears to be a dose-dependent phenomenon, it may be more important in poor metabolizers of CYP2C19 who have more than four rimes the area under the lansoprazole plasma concentration-time curve (AUC) and constitute 12% to 23% of Asianpopulations. Theophylline owes a significant portion of its metabolism to CYP1A2 and can cause gastric acid reflux that calls for concurrent use of proton pump inhibitors, We conducted a prospective, randomized, subject-blind, multicenter crossover study of the effect of multiple high-dose oral lansoprazole (30 mg twice a day for 7 days) on the pharmacokinetics of a single intravenous dose of theophylline (4.73 mg/kg) in healthy volunteers characterized for CYP2C19 genotype, The study compared the pharmacokinetics of lansoprazole and theophylline in five white extensive metabolizers, six Korean extensive metabolizers, and seven poor metabolizers of CYP2C19, The pharmacokinetics of lansoprazole were significantly different among groups; AUCvalues were 1.55 +/- 0.20 mu g.h/mL in white extensive metabolizers, 7.01 /- 0.72 mu g.hr/mL in Korean extensive metabolizers, and 14.34 +/- 2.60 mug.h/mL in poor metabolizers (P < .001), The administration of lansoprazoledid not change intravenous theophylline clearance compared with placebo inany group, and theophylline clearance exhibited no correlation with AUC oflansoprasole (r(s) = 0.12; P > .1), These data suggest that usual therapeutic doses of lansoprazole have no clinically significant influence on the clearance of theophylline, even in poor metabolizers of CYP2C19.

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Documento generato il 26/01/20 alle ore 01:08:01