Local view for "https://dbmi-icode-01.dbmi.pitt.edu/dikb/resource/Evidence/114"
| Predicate | Value (sorted: default) |
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| rdfs:label | |
| rdf:type | |
| ?:Evidence_enzyme_system | |
| ?:Evidence_numb_subjects | |
| ?:Evidence_object_dose | |
| ?:Evidence_precip_dose | |
| ?:Evidence_type | |
| ?:Evidence_value | |
| ?:content |
"NOTE: The AUC_i/AUC value is for the group that took 150mg of fluvoxamine and is calculated from Table I.
route of administration: oral
study duration: 5 days
population: 14 healthy volunteers, all male
tested for known CYP450 polymorphisms?
NO
ages: 21-30
description:
SUBJECTS: The study was carried out as an open, randomized, crossover design. The participants were 14 volunteers; all of the participants were men with a median age of 26 years (range, 21 to 30 years). The subjects had no known heart, liver, or kidney disease according to a clinical examination, clinical chemical and hematologic screening, and electrocardiogram. No participants consumed alcohol or drugs on a regular basis at the time of the study. The volunteers consented to participate in the study on the basis of oral and written information.
METHODS: The study was divided into two periods. In period A, all volunteers took 500 mg of tolbutamide (Tolbutamide “DAK�, Nycomed Denmark, Roskilde, Denmark) as a single oral dose. In period B, the volunteers were randomly assigned to two fluvoxamine groups. One group took 150 mg/d of fluvoxamine (Fevarin 100-mg tablets, Solvay Duphar BV, Weesp, The
Netherlands) for 5 days with a single oral dose of 500 mg of tolbutamide. The other group took a dose of 75 mg of fluvoxamine for 5 days and a single oral dose of 500 mg of tolbutamide. Period A and period B were separated by at least 1 week. Fluvoxamine was given at 20.00 hours.
RESULTS: Total tolbutamide (TB) clearance (CL_TB) was calculated as follows: CL_TB = Dose/AUC in which AUC is the area under the plasma concentration-time curve calculated by means of the trapezoidal rule with extrapolation from the last measurable concentration to infinity. Complete absorption of tolbutamide from the intestine was assumed.
The mean plasma concentration of tolbutamide versus time after a single oral dose of 500 mg of tolbutamide before (period A) and during (period B) concomitant intake of 150 mg/d or 75 mg/d of fluvoxamine is shown in Fig 2. The results of the pharmacokinetic analysis are listed in Table I. Thus the median values of the total clearance of tolbutamide were 845 and 962 mL/h in the group that received 75 mg and the group that received 150 mg, respectively, before the administration of fluvoxamine. During fluvoxamine intake, the clearance values decreased to 688 and 642 mL/h, respectively, and the decrease was statistically significant both in the group that received 75 mg and in the entire group (75 mg and 150 mg) but not in the group that received 150 mg alone. The picture was even more clear for the hydroxylation clearance, for which there was a statistically significant reduction as judged from 95% confidence intervals for the median difference not comprising zero both in the 75-mg and 150-mg fluvoxamine groups. There was a tendency toward a more marked reduction in the latter group, although the difference between the two groups (150 mg versus 75 mg in period B) did not reach a level of statistical significance (Table I).
See Table I and the equation CL_TB = Dose/AUC for more information. The AUC_i/AUC for the 150mg dose was 1.50 and for the 75mg dose was 1.22."
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| dc:creator | |
| dc:date |
"09/22/2010 12:59:40"
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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_tolbutamide, <http://purl.org/swan/1.2/swan-commons#citesAsSupportingEvidence>, evidence_1873 }