Local view for "https://dbmi-icode-01.dbmi.pitt.edu/dikb/resource/Evidence/1433"
| Predicate | Value (sorted: none) |
|---|---|
| rdf:type | |
| rdf:type | |
| rdfs:label | |
| ?:Evidence_type | |
| ?:Evidence_enzyme_system | |
| ?:Evidence_object_dose | |
| ?:Evidence_precip_dose | |
| ?:Evidence_value | |
| dc:creator | |
| dc:date |
"02/16/2012 21:55:54"
|
| ?:content |
"NOTE: The AUC_i/AUC given is for EMs and calculated from Table 2 using the formula AUC = dose/Cl
route of administration: oral
study duration: 2 days
population: 15 healthy men, all nonsmokers
tested for known CYP450 polymorphisms?
YES - CYP2D6 phenotyping -- 9 EMs (7 CYP2D6*1/*1, 2 CYP2D6*1/*4), 6 PMs (1 CYP2D6*3/*4, 4 CYP2D6*4/*4, 1 CYP2D6*7/*7)
ages: average age 27 +/- 5
description:
SUBJECTS: Fifteen healthy men (nine EMs and six PMs) participated in the study. Their mean (+/-SD) age was 27 +/- 4 years and 27 +/- 5 years, and their mean body weight was 71 +/- 8 kg and 84 +/- 11 kg for EMs and PMs, respectively (Table 1). All volunteers were nonsmokers and healthy as determined by routine physical examination, electrocardiogram, and laboratory tests.
METHODS: Subjects received oral doses (N = 5) of 18.75 mg venlafaxine hydrochloride (Effexor, Wyeth-Ayerst Canada, Inc., Montreal, Canada) every 12 hours for 48 hours on two occasions: once alone and once during the concomitant administration of 50 mg of diphenhydramine hydrochloride (Benadryl, Warner Wellcome, Scarborough, Canada) every 12 hours. Diphenhydramine was also administered alone and during concomitant administration of venlafaxine. The three study arms were performed 1 week apart. Venlafaxine tablets were prepared by the Department of Pharmacy, Laval Hospital, by cutting 37.5-mg venlafaxine hydrochloride tablets in half. No other drugs, caffeine-containing foods or beverages, chocolate, or alcohol were allowed 48 hours before and during the study.
RESULTS: When venlafaxine was administered alone, mean
AUC0–12 values for all subjects studied were 3.1 +/- 2.2 umol.hr-1.L-1 in PMs and 0.8 +/- 0.6 umol.hr-1.L-1 in EMs, respectively ( p < 0.05). The right panels of Figure 2 illustrate plasma concentrations of venlafaxine measured after the oral administration of venlafaxine during concomitant administration of diphenhydramine in the same PM and EM. Coadministration of diphenhydramine did not alter the plasma concentrations of venlafaxine in the PM. In contrast, diphenhydramine increased the AUC0–12 of venlafaxine more than 4-fold in the EM, leading to values toward those measured in the PM subject. On average, diphenhydramine increased venlafaxine AUC0–12 by more than 2-fold in EMs ( p < 0.05).
Figure 3 and Table 2 report the pharmacokinetic parameters observed in EMs and PMs on venlafaxine alone and during concomitant administration of diphenhydramine. The mean oral clearance of venlafaxine was more than 4-fold greater in EMs compared with PMs when venlafaxine was administered alone. In EMs, coadministration of diphenhydramine decreased oral clearance of venlafaxine by more than 2-fold ( p < 0.05), leading to values close to those measured in PMs. In contrast, coadministration of diphenhydramine did not affect the oral clearance of venlafaxine in PMs."
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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:
{ diphenhydramine_increases_auc_venlafaxine, <http://purl.org/swan/1.2/swan-commons#citesAsSupportingEvidence>, evidence_1866 }