Local view for "https://dbmi-icode-01.dbmi.pitt.edu/dikb/resource/Evidence/1425"
| 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 |
"05/05/2009 16:05:09"
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| ?:content |
"Route of administration: oral (inferred because IV formulations do not appear to be available for paroxetine and desipramine)
study duration: see below
population: 17 volunteers (design called for 24 but several dropped out or were excluded due to non-compliance); all participants were extensive metabolizers of dextromethorphan (o-demethylation)
ages: mean(std dev): 30.4 (+/-5.2)
AUC_i/AUC (24 hour): 3305 / 634 = 5.2
NOTE: AUC increase mentioned is for the phase of the study using 20mg of paroxetine.
Description:
The pharmacokinetics of desipramine when coadministered with the selective serotonin reuptake inhibitors (SSRIs) paroxetine and sertraline were studied in 24 healthy male volunteers (CYP2D6 extensive metabolizers). Desipramine (50 mg/day) was administered for 23 days in each phase of the crossover study with a 7-day drug-free period between phases. In addition, subjects were randomly assigned to receive concomitant paroxetine (20 mg/day on days 8 through 17 followed by 30 mg/day on days 18 through 20) or sertraline (50 mg/day on days 8 through 17 and 100 mg/day on days 18 through 20). SSRI treatments were switched between phases. After 10 days of coadministration at the lower dose, mean desipramine maximum concentration in plasma (Cmax) relative to baseline increased from 37.8 to 173 ng/mL (+358%) with paroxetine versus from 36.1 to 51.9 ng/mL (+44%) with sertraline; the mean desipramine 24-hour area under the concentration-time curve (AUC[24]) increased from 634 to 3,305 ng x h/mL (+421%) with paroxetine versus from 611 to 838 ng x h/mL (+37%) with sertraline; and the mean desipramine trough value (C0) increased from 18.5 to 113 ng/mL (+511%) with paroxetine versus from 18.3 to 21.8 ng/mL (+19%) with sertraline (all increases, p < 0.001). An approximately 10-fold increase in the Cmax and AUC(24) of paroxetine and an approximately 2-fold increase in these parameters for sertraline occurred simultaneously with the desipramine concentration changes. Thus, when coadministered with 50 mg/day desipramine, sertraline had significantly less pharmacokinetic interaction than paroxetine with desipramine at the recommended starting dosages of 50 mg/day and 20 mg/day, respectively."
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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_desipramine, <http://purl.org/swan/1.2/swan-commons#citesAsSupportingEvidence>, evidence_1222 }