A change in the metabolism of one probe drug cannot be assumed for all medicines processed by the liver.
What the supplied source reports
Twelve healthy volunteers completed a randomized crossover experiment comparing overnight fasting with thirty-six-hour fasting. An oral and intravenous probe cocktail included midazolam, caffeine, metoprolol, omeprazole and warfarin. The reported significant clearance changes involved caffeine, metoprolol and S-warfarin, while oral bioavailability was not affected.
Limits of the evidence
The sample was small and healthy, and a brief controlled fast differs from chronic malnutrition or critical illness. The results were pathway-specific. The presence of midazolam in the cocktail does not mean the study demonstrated a significant fasting effect for that drug.
Implications for forensic interpretation
For a pharmacokinetic opinion, identify the specific enzyme pathway and measured parameter before generalizing. Distinguish clearance from absorption and bioavailability. This study cannot supply a universal fasting correction for benzodiazepine concentration or convert nutritional history alone into an explanation for excessive sedation.
Source and related reading
Source reviewed: Effect of Short Term Fasting on Systemic Cytochrome P450 Mediated Drug Metabolism in Healthy Subject (PMC5591816). Forensic applications above are interpretive analysis of the supplied publication.
Related reading: A Mixed Midazolam–Propofol Comparison Cannot Identify Midazolam’s Independent Mortality Effect.
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