Local view for "https://dbmi-icode-01.dbmi.pitt.edu/dikb/resource/Evidence/1003"
| Predicate | Value (sorted: default) |
|---|---|
| rdfs:label |
"evidence_1072"
|
| rdf:type | |
| ?:Evidence_enzyme_system | |
| ?:Evidence_numb_subjects | |
| ?:Evidence_object_dose | |
| ?:Evidence_precip_dose | |
| ?:Evidence_type | |
| ?:Evidence_value | |
| ?:content |
"NOTE: The AUC_i/AUC is from the heterozygous EMs and calculated from Table 1.
route of administration: oral
study duration: 6 days
population: 18 healthy volunteers (9 male, 9 female), all Japanese
tested for known CYP450 polymorphisms?
Yes -- CYP2C19 genotypes - 6 homozygous EMs, 6 heterozygous EMs, 6 homozygous PMs
ages: mean 25.1 years (+/- 3.8)
description:
Eighteen healthy Japanese volunteers (9 men and 9 women) who were H. pylori-negative were enrolled in this study. Their mean age was 25.1 +/- 3.8 years and mean body weight was 56.6 +/- 13.3 kg. Most subjects in this study had participated in our previous studies. The mutated alleles for CYP2C19, CYP2C19*3(*3), and CYP2C19*2(*2) had been identified using polymerase chain reaction-restriction fragment length polymorphism methods of De Morais et al, before this study. The CYP2C19 genotype analyses revealed 5 different patterns as follows: *1/*1 in 6, *1/*2 in 3, *1/*3 in 3, *2/*2 in 5, and *2/*3 in 1. These were divided into 3 groups, homozygous EMs (*1/*1, n=6), heterozygous EMs (*1/*2 and *1/*3, n=6), and PMs (*2/*2 and *2/*3, n=6).
METHODS: A randomized double-blind placebo-controlled crossover study design in 3 phases was conducted at intervals of 2 weeks. Clarithromycin (400 mg) as a capsule containing the equivalent of 2 tablets, fluvoxamine (25 mg) as a capsule containing the equivalent of a tablet, or matched placebo was given orally twice a day (9 AM, 9 PM) for 6 days. Six volunteers within each group were allocated to each of the 3 different drug sequences: placebo-clarithromycin-fluvoxamine, fluvoxamine-placebo-clarithromycin, or clarithromycin-fluvoxamine-placebo. On day 6, they took a single oral 60-mg dose of lansoprazole with 400 mg dose of clarithromycin, 25mg dose of fluvoxamine, or placebo after overnight fasting (9 AM). No other medications were taken during the study periods. No meal was allowed until 4 hours after the dosing (1 PM). The use of alcohol, tea, coffee, and cola was forbidden during the test days.
RESULTS: Clarithromycin treatment significantly increased Cmax and AUC_0-24 of lansoprazole in heterozygous EMs (P<0.05) and in PMs (P<0.01), and prolonged elimination half-life by 1.6-fold (P<0.05) in PMs. Calculated from Table 1, the AUC_i/AUC were: 1.62 (homozygous EMs), 1.71 (heterozygous EMs [p<0.05]), and 1.89 (PMs [p<0.01])."
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| dc:creator | |
| dc:date |
"08/23/2010 13:04:42"
|
| rdfs:seeAlso |
All properties reside in the graph file:///home/swish/src/ClioPatria/guidelines/dikb.ttl
The resource appears as object in one triple:
{ clarithromycin_increases_auc_lansoprazole, <http://purl.org/swan/1.2/swan-commons#citesAsSupportingEvidence>, evidence_1072 }