FORENSIC TOXICOLOGY

A drug interaction study can report a higher peak concentration, greater total exposure or both. Those measures answer different questions about the concentration curve.

Two endpoints from one probe experiment

Armani and colleagues administered a cocktail of metabolic probes to healthy adults before and after a single 50 mg osilodrostat dose. Nineteen participants completed the study. Midazolam served as a CYP3A4/5 probe. Its geometric mean exposure ratio for area under the curve through the last measurable concentration was 1.50, with a 90% confidence interval of 1.41 to 1.60. The corresponding ratio for peak concentration was 1.47, with a 90% interval of 1.32 to 1.62.

Use the exposure window explicitly

Area under the curve summarizes exposure across the observed concentration-time profile. The peak reflects the highest sampled concentration. This comparison followed a particular single-dose sequence in healthy adults. Applying the ratios to a different medication, repeated dosing or a patient with different organ function requires additional evidence. An isolated midazolam measurement supplies neither the area under the curve nor assurance that the specimen was collected at the peak.

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