Local view for "https://dbmi-icode-01.dbmi.pitt.edu/dikb/resource/Evidence/873"
| Predicate | Value (sorted: default) |
|---|---|
| rdfs:label |
"evidence_1477"
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| rdf:type | |
| ?:Evidence_enzyme_system | |
| ?:Evidence_numb_subjects | |
| ?:Evidence_object_dose | |
| ?:Evidence_precip_dose | |
| ?:Evidence_type | |
| ?:Evidence_value | |
| ?:content |
"NOTE: The AUC_i/AUC is from the AUC_0-inf of all the subjects taken together, not separated by genotype.
route of administration: oral
study duration: 4 days
population: 12 healthy volunteers (all male), all nonsmokers
tested for known CYP450 polymorphisms? Yes -- CYP2D6 genotypes - 8 EMs, 1 PM, 3 UMs
ages: 20-29
description: 12 male volunteers (age range: 20–29 years; weight range: 65–89 kg) were recruited. The subjects were ascertained to be in good health by medical history, physical examination, and standard hematological and clinical chemistry tests. All subjects were non-smokers and used no concomitant medications.
All 12 subjects completed the study according to the protocol. Genotyping of CYP2D6 revealed that eight subjects could be classified as EMs: six of them were homozygous for CYP2D6*1 allele, and two of them had the genotype CYP2D6*1/*4. One subject was classified as PM having the CYP2D6*3/*4 genotype, and three subjects without *3 or *4 were classified as UMs having a CYP2D6*1/*1x2 genotype. This high frequency of UM (25%) was much more than expected, but the subjects were not selected for the study by genotype.
METHODS: The study was an open-label, randomized, three-phase crossover study with a washout period of 4 weeks between the phases. The volunteers were given either no pretreatment (control phase) or oral terbinafine (terbinafine phase) for 4 days in a randomized order. The dose of terbinafine (Lamisil 250mg tablet; Novartis Pharma, Huningue, France) was 250mg once a day at 0800 hours for 4 days. Terbinafine were self-administered by subjects except for the last doses, which were administered by the study personnel.
One hour after the last dose of terbinafine was ingested, all volunteers received 75 mg oral dose of venlafaxine (Efexor 75 mg tablet; Wyeth Pharmaceuticals, New Lane, Havant, Hants, England) at 0900 hours with 150 ml of water. During all phases, the subjects fasted overnight before administration of venlafaxine and continued fasting until a standardized lunch was served 4 h after venlafaxine ingestion. The subjects were forbidden to use any other medication for 14 days before and during the study and any drug known to cause enzyme induction or inhibition for a period of 30 days before the study. Caffeine, grapefruit juice, and alcohol-containing beverages were not allowed during the study.
RESULTS: When all the subjects were examined together, without subdivision into groups according to the genotype, terbinafine pretreatment increased the area under the plasma concentration–time curve (AUC_0–inf) of venlafaxine 4.9-fold (range: 1.5- to 8.2-fold; P<0.001)."
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| dc:creator | |
| dc:date |
"09/01/2010 15:40:49"
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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:
{ terbinafine_increases_auc_venlafaxine, <http://purl.org/swan/1.2/swan-commons#citesAsSupportingEvidence>, evidence_1477 }