Bess M Kew, Matthew P Doogue, Richard McNeill, Mei Zhang, Julia J Rucklidge, Christopher M Frampton, Roger T Mulder, Ben Beaglehole
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引用次数: 0
Abstract
Aims: Daily broad-spectrum micronutrients are being used by the general public and formulations are receiving research interest in mental health settings. Despite concerns about combining medicines and broad-spectrum micronutrients in mental health care, there have not been any formal evaluations of potential interactions. Our objective was to evaluate a broad-spectrum micronutrient formula as a potential precipitant of pharmacokinetic drug-drug interactions through inhibition or induction of cytochrome P450 (CYP) enzymes.
Methods: This was a single-centre pharmacokinetic study. Twelve healthy participants received broad-spectrum micronutrients for 14 days (Days 1-14). Participants were administered a 'cocktail' of selective CYP probes midazolam 2 mg (CYP3A), dextromethorphan 30 mg (CYP2D6), losartan 25 mg (CYP2C9), omeprazole 20 mg (CYP2CI9) and caffeine 100 mg (CYP1A2) on Day 0 and Day 14, before taking and while taking broad-spectrum micronutrients. Plasma drug concentrations were measured at baseline and for 8 h following cocktail administration. AUC, Cmax and Tmax were compared before and after broad spectrum micronutrient administration using paired t-tests.
Results: Pre- and post-micronutrient geometric means (SD) for AUC0-8h (μg*h/L) were: midazolam 25 (13) and 26 (14), P = 0.60; dextromethorphan 25 (99) and 19 (110), P = 0.46; losartan 219 (105) and 205 (76), P = 0.20; omeprazole 474 (394) and 402 (342), P = 016; and caffeine 13 800 (5400) and 12 800 (3500), P = 0.79. There were no statistically significant changes in geometric means of probe Cmax, or Tmax for any of the study drugs.
Conclusions: Broad-spectrum micronutrients are unlikely to be a major precipitant of pharmacokinetic drug-drug interactions.
期刊介绍:
Published on behalf of the British Pharmacological Society, the British Journal of Clinical Pharmacology features papers and reports on all aspects of drug action in humans: review articles, mini review articles, original papers, commentaries, editorials and letters. The Journal enjoys a wide readership, bridging the gap between the medical profession, clinical research and the pharmaceutical industry. It also publishes research on new methods, new drugs and new approaches to treatment. The Journal is recognised as one of the leading publications in its field. It is online only, publishes open access research through its OnlineOpen programme and is published monthly.