Local view for "https://dbmi-icode-01.dbmi.pitt.edu/dikb/resource/Evidence/1227"
| Predicate | Value (sorted: none) |
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| rdf:type | |
| rdf:type | |
| rdfs:label | |
| ?:Evidence_type | |
| ?:Evidence_enzyme_system | |
| ?:Evidence_numb_subjects | |
| ?:Evidence_object_dose | |
| ?:Evidence_precip_dose | |
| ?:Evidence_value | |
| dc:creator | |
| dc:date |
"09/22/2010 11:27:10"
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| ?:content |
"NOTE: The AUC_i/AUC value is calculated from Table 1 using the formula CL = dose / AUC
route of administration: oral
study duration: 5 days
population: 6 young healthy volunteers (all male)
tested for known CYP450 polymorphisms?
YES -- CYP2D6 and CYP2C19 phenotyping - All extensive metabolizers
ages: none given
description:
SUBJECTS: This was an open study of six young healthy male volunteers, all phenotyped as extensive metabolisers of sparteine (CYP2D6) (metabolic ratio < 20) and mephenytoin (CYP2C19) (S/R ratio < 0.5). All volunteers gave written informed consent. The study was approved by the regional ethics committee and the Danish National Board of Health. Before inclusion, all volunteers were screened by physical examination, laboratory tests and electrocardiogram.
METHODS: On study day 1, the volunteers took a single oral dose of 250 mg tolbutamide (CYP2C9) (Tolbutamid ''Dak'', Nycomed DAK, Denmark) at 0800 hours. On study day 2, the volunteers took 100 mg sparteine (CYP2D6) (Depasan, Giulini Pharma, Germany), 100 mg mephenytoin (CYP2C19) (Mesantoin, Sandoz Pharmaceuticals, USA) and 200 mg caffeine (CYP1A2) (Koffein ''Dak'', Nycomed DAK) orally at 0800 hours.
On study day 3, following an overnight fast from 2400 hours, the volunteers took a single oral dose of 200 mg quinidine sulfate (Kinidin ''Dak'', Nycomed DAK), equivalent to 511 umol quinidine. The volunteers were allowed normal meals after the blood sample at t = 1 h was drawn. Following a washout period of 6-8 weeks, the volunteers took 100 mg of fluvoxamine (Fevarin, Solvay Duphar, Netherlands) daily at 0800 hours on study days -1, 0, 1, 2, 3 and 4. The study procedures on days 1-4, above, were repeated. During the study, the volunteers refrained from intake of any other medications, alcohol or grapefruit juice. Consumption of coffee or xanthine-containing foods was not allowed for a period of 48 h before and the 12 h during caffeine testing. The quinidine and the quinidine and fluvoxamine sessions were performed without randomisation of the sequence, justified by only using hard end-points, i.e. drug- and metabolite-concentrations in plasma and urine, in the study.
RESULTS: The total apparent oral clearance of quinidine was calculated as: CLq = Dose / AUCq (0 -> inf). The quinidine total apparent oral clearance, clearance by N-oxidation and by 3-hydroxylation were statistically significantly reduced during fluvoxamine treatment by medians of 29%, 33% and 44%, respectively.
See Table 1 and formula."
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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_quinidine, <http://purl.org/swan/1.2/swan-commons#citesAsSupportingEvidence>, evidence_1512 }