Local view for "https://dbmi-icode-01.dbmi.pitt.edu/dikb/resource/Evidence/665"
| 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 |
"08/23/2010 15:39:12"
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| ?:content |
"NOTE: AUC_0-24 is used for AUC_i/AUC.
route of administration: oral
study duration: 27 days
population: 20 healthy subjects (11 male, 9 female)
tested for known CYP450 polymorphisms?
Yes -- CYP2D6 - all were extensive metabolizers
ages: 18-45
description:
SUBJECTS
Twelve healthy male and twelve healthy female subjects aged between 18 and 45 years participated in this three-period crossover study. They were extensively screened within 3 weeks of study entry and had to be medically and mentally healthy, as evidenced by medical history, full physical examination, routine clinical laboratory investigations and ECG. Their body mass index had to be within the range 19-29 kg/m2 and they were not allowed to be smokers. Subjects were screened for being extensive metabolizers of CYP2D6 using dextromethorphan as a probe.
Of the 12 males and 12 female subjects enrolled into the study, three subjects (1 male, 2 females) discontinued the study due to the emergence of adverse events on days 21, 23, and 27, respectively, of the 27 day treatment period.
METHODS
Subjects meeting the inclusion criteria were enrolled into the study. They were randomly assigned to one of six treatment sequences in this three-period crossover study without washout intervals. They were admitted to the clinical pharmacology institute two days before the start of the study. In order to mimic clinical practice as much as possible, paroxetine was administered in the morning and mirtazapine in the evening, with a 12h interval between administrations. From day 1 up to and including day 26 paroxetine 20 or 40 mg or placebo was administered at 9 a.m. and mirtazapine 15 or 30 mg or placebo at 9 p.m. each day.
The treatments used were: (A) 20 mg paroxetine plus one placebo paroxetine capsule at 9 a.m. and two placebo mirtazapine tablets at 9 p.m. for the first three days followed by two 20 mg paroxetine capsules at 9 a.m. and two placebo mirtazapine tablets at 9 p.m. for the following 6 days; (B) two placebo paroxetine capsules at 9 a.m. and one 15 mg mirtazapine plus one placebo mirtazapine tablet at 9 p.m. for 3 days followed by two placebo paroxetine capsules at 9 a.m. and two 15 mg mirtazapine tablets at 9 p.m. for the following 6 days; (C) 20 mg paroxetine plus one placebo paroxetine capsule at 9 a.m. and 15 mg mirtazapine plus one placebo mirtazapine tablet at 9 p.m. for 3 days followed by two 20 mg paroxetine at 9 a.m. and two 15 mg mirtazapine at 9 p.m. for the following 6 days. Thus, six possible treatment sequences (TS1 - TS6) were used (Table 1). In those treatment sequences in which either paroxetine or mirtazapine had also been administered in the preceding treatment sequence, the drug was continued at the highest dose, i.e. two 20 mg capsules for paroxetine and two 15 mg tablets for mirtazapine. Two males and two females were randomized to each of the six treatment sequences.
RESULTS
Adding paroxetine to mirtazapine treatment increased the mirtazapine plasma concentrations. The AUC_0-24 increased by approximately 17% during concomitant administration of paxoetine. Statistically significant differences were observed in AUC_0-24 and C_max,av."
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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:
{ paroxetine_increases_auc_mirtazapine, <http://purl.org/swan/1.2/swan-commons#citesAsSupportingEvidence>, evidence_1906 }