Abstract:
BACKGROUND:Cytochrome P450 3A is the most relevant drug-metabolizing enzyme in humans as it is involved in the elimination of 50% of marketed drugs. Nothing is known about the activity of cytochrome P450 3A in palliative care patients who have complicated symptoms often associated with a terminal illness. AIM:In order to improve drug dosing in end-of-life care and to avoid drug interactions, cytochrome P450 3A activity was determined in patients of a palliative care unit under real-life clinical conditions. DESIGN:As midazolam is an established marker substance for cytochrome P450 3A activity, this single-arm prospective trial was designed to obtain a 4-h pharmacokinetic profile of midazolam after oral administration of a 10-µg dose from each enrolled patient. Plasma concentrations of midazolam and its primary metabolite 1'-hydroxy-midazolam were quantified by mass spectrometry techniques. Cytochrome P450 3A activity was calculated as partial metabolic clearance from a limited sampling area under the curve. All other drugs taken by the participating patients were considered, as well as recent blood test results and patients' diagnoses. The trial was registered at German Clinical Trials Register ( www.drks.de ): DRKS00011753. SETTING/PARTICIPANTS:The trial was carried out at a university palliative care unit under real-life clinical conditions. Every patient admitted to the ward was screened for possible participation, independent of the individual performance status. RESULTS:Partial metabolic clearance of midazolam in palliative care patients was 31.7 ± 32.1 L/h. This was a highly significant 40% reduction (p < 0.0001) in comparison with the cytochrome P450 3A activity of healthy subjects. CONCLUSION:Dosing of cytochrome P450 3A substrate drugs (e.g. macrolide antibiotics, benzodiazepines, calcium channel blockers) needs to be adjusted in palliative care patients; otherwise, escalation of debilitating symptoms due to drug interactions might occur.
journal_name
Palliat Medjournal_title
Palliative medicineauthors
Geist M,Bardenheuer H,Burhenne J,Mikus Gdoi
10.1177/0269216319843629subject
Has Abstractpub_date
2019-07-01 00:00:00pages
850-855issue
7eissn
0269-2163issn
1477-030Xjournal_volume
33pub_type
杂志文章abstract:BACKGROUND:The majority of children and young people who die in the United Kingdom have pre-existing life-limiting illness. Currently, most such deaths occur in hospital, most frequently within the intensive care environment. AIM:To explore the experiences of senior medical and nursing staff regarding the challenges a...
journal_title:Palliative medicine
pub_type: 杂志文章
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journal_title:Palliative medicine
pub_type: 杂志文章,多中心研究
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journal_title:Palliative medicine
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