Local view for "https://dbmi-icode-01.dbmi.pitt.edu/dikb/resource/Evidence/134"
| Predicate | Value (sorted: none) |
|---|---|
| rdf:type | |
| rdf:type | |
| rdfs:label |
"evidence_1918"
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| ?:Evidence_type | |
| ?:Evidence_enzyme_system | |
| ?:Evidence_numb_subjects | |
| ?:Evidence_object_dose | |
| ?:Evidence_precip_dose | |
| ?:Evidence_value | |
| dc:creator | |
| dc:date |
"09/22/2010 14:41:01"
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| ?:content |
"NOTE: The AUC_i/AUC value given is calculated from Table 1. The precip_dose given is the mean dose (+/- 0.866)
route of administration: oral
study duration: 22 days
population: 5 volunteers with major affective disorders (DSM-III-R criteria), (2 male, 3 female)
tested for known CYP450 polymorphisms?
NO
ages: mean age 40.4 +/- 11.5
description:
SUBJECTS: Patients meeting DSM-III-R criteria for major affective disorders were admitted to the 3-West Clinical Research Unit of the Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland. Patients volunteered to participate in the clinical research program and gave oral and written informed consent for clinical trials of CBZ, VPA, and BUP, as well as other medications and associated research procedures. A thorough medical and neurologic history and examination and a pretreatment electroencephalogram were done to rule out the presence of seizure disorders and other medical illnesses. A detailed life course of illness was visually plotted and quantified for each patient as previously described. Psychiatric diagnoses were confirmed by the Schedule for Affective Disorders and Schizophrenia structured diagnostic interview. Thus, these patients were carefully characterized as having primary mood disorders (for the purpose of assessing clinical responses to medications) and lacking concurrent medical disorders that could alter pharmacokinetics. Patients and nursing staff were blind to chronic medications, as well as to the pharmacokinetic study drug being administered, in order to allow a more objective assessment of clinical responses. The blind condition was also maintained with patients and nurses by having blind "CBZ" and "VPA" concentrations drawn throughout the hospitalization, even at times when patients were not receiving either drug.
The placebo and VPA groups did not differ significantly with respect to mean age (placebo, 38.5 +/- 10.2; VPA, 40.4 +/- 11.5) or gender (placebo, eight men and nine women; VPA, two men and three women). Four patients had both placebo and VPA studies.
METHODS: Patients had 24-hour pharmacokinetic profiles of BUP and metabolites after single oral doses of BUP, 150 mg, while receiving placebo (N = 17) or during chronic VPA (N = 5) monotherapy. Patients were on VPA for at least 3 weeks in order to allow dosage titration and the attainment of steady state. Patients on VPA received a mean dose of 1,750 +/- 866 mg/day with a mean trough VPA concentration in plasma of 97 +/- 19 micro gram/ml. Single trough VPA concentrations in plasma were determined during the week of the kinetic study for each patient on these agents.
For each pharmacokinetic study, a single oral dose of BUP, 150 mg, was administered at 9 a.m. in a blind fashion. Patients had nothing by mouth from 11:30 p.m. the night before until 3 hours after receiving the blind BUP dose, at which point they resumed their blinded placebo or VPA and their usual oral intake of food and fluids. Patients were receiving VPA in three or four divided doses each day and missed at most a single morning dose of VPA, so that the concentrations of these agents in plasma were maintained during the kinetic studies.
RESULTS: CBZ but not VPA therapy decreased BUP C_max by 87% (p <0.0001) and 24-hour AUC by 90% (p < 0.0001) (Table 1; Figure 2). These findings were similar in paired analyses of the seven patients who had studies both on placebo and CBZ (CBZ decreased C_max by 81% [p = 0.0005] and AUC by 84% [p = 0.0003]) and the four patients with studies both on placebo and VPA. Five (42%) of 12 patients on CBZ had no detectable BUP concentrations at all times sampled, whereas no patients on placebo or VPA had such null profiles. There was a trend toward an earlier time of BUP C_max (T_max) on VPA (1.1 +/- 0.2 hours) than on placebo (1.7 +/- 0.8 hours, p < 0.10) that was also evident in the four patients with studies both on placebo and VPA (p < 0.07)."
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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:
{ valproate_increases_auc_bupropion, <http://purl.org/swan/1.2/swan-commons#citesAsRefutingEvidence>, evidence_1918 }