Local view for "https://dbmi-icode-01.dbmi.pitt.edu/dikb/resource/Evidence/918"
| Predicate | Value (sorted: none) |
|---|---|
| rdf:type | |
| rdf:type | |
| rdfs:label |
"evidence_1652"
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| ?:Evidence_type | |
| ?:Evidence_enzyme_system | |
| ?:Evidence_numb_subjects | |
| ?:Evidence_object_dose | |
| ?:Evidence_precip_dose | |
| ?:Evidence_value | |
| dc:creator | |
| dc:date |
"09/15/2010 15:02:35"
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| ?:content |
"NOTE; The precipitant drug dose is the Period 3 dose of the EMs. The AUC_i/AUC is the combined (both EMs and PMs) AUC_0-8h of Period 3.
route of administration: oral
study duration: Period 1 - 3 days, Periods 2 and 3 - 7 days
population: 10 healthy volunteers, all Caucasian, all nonsmokers
tested for known CYP450 polymorphisms?
Yes -- CYP2D6 phenotyping - 5 extensive metabolizers, 5 poor metabolizers
ages: 22-45
description:
SUBJECTS: Twelve healthy white subjects, 6 men and 6 women, aged 22 to 45 years (mean, 30 years) and weighing 56 to 94 kg (mean, 81 kg for the men and 69 kg for the women), participated in this study, which included 7 EMs and 5 PMs of debrisoquin. The debrisoquin metabolic ratio (MR) ranged from 0.57 to 2.2 in EMs and from 35 to 260 in PMs. Genotyping of CYP2D6 and CYP2C19 was performed in 1 subject (subject No. 12) by the methods of Heim and Meyer (CYP2D6*3 and *4) and de Morais et al (CYP2C19*2). All subjects were healthy as assessed by medical history, physical examination, urine drug screen, standard 12-lead electrocardiogram, virologic testing, and routine laboratory analyses. All were nonsmokers and had been drug-free for at least 1 week before the study.
Two EM subjects (subjects No. 1 and No. 4) were not able to participate in period 3 because of travel abroad and, therefore, were replaced by 2 new EMs (subjects No. 12 and No. 13). They also followed the protocol in period 1 before entering period 3.
METHODS: Single oral doses of 100 mg caffeine and 20 mg omeprazole were given separately to 5 EMs and 5 PMs of debrisoquin to assess the activity of CYP1A2 and CYP2C19, respectively. Initially, a single oral dose of fluvoxamine (25 mg to PMs and 50 mg to EMs) was given [Period 1], followed by 1 week of daily administration of 25 mg × 2 to EMs and 25 mg × 1 to PMs [Period 2]. Caffeine (day 6) and omeprazole (day 7) were again administered at the steady state of fluvoxamine. Later the study protocol was repeated with a lower dose of fluvoxamine, 10 mg × 2 to EMs and 10 mg × 1 to PMs for 1 week [Period 3]. Concentrations of fluvoxamine, caffeine, omeprazole, and their metabolites were analyzed by HPLC methods in plasma and urine.
Because fluvoxamine kinetics is partly dependent on the polymorphic enzyme CYP2D6, we gave double the dose of fluvoxamine to EMs of debrisoquin compared with PMs of debrisoquin to obtain similar plasma concentrations of fluvoxamine.
RESULTS: The geometric means of omeprazole AUC(0-8 h) increased with 174% (P < .001) with 10 mg x 1 or x 2 [Period 3] and 330% (P < .001) with 25 mg x 1 or × 2 of fluvoxamine [Periods 1-2]."
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| rdfs:seeAlso |
All properties reside in the graph file:///home/swish/src/ClioPatria/guidelines/dikb.ttl
The resource appears as object in one triple:
{ fluvoxamine_increases_auc_omeprazole, <http://purl.org/swan/1.2/swan-commons#citesAsSupportingEvidence>, evidence_1652 }