Intraindividual Variability in Absolute Bioavailability and Clearance of Midazolam in Healthy Individuals
In: Clin Pharmacokinet, 2023
academicJournal
Zugriff:
BACKGROUND AND OBJECTIVE: Midazolam is the preferred clinical probe drug for assessing CYP3A activity. We have previously shown substantial intraindividual variability in midazolam absolute bioavailability and clearance in patients with obesity before and after weight loss induced by gastric bypass or a strict diet. The objective was to describe intraindividual variability in absolute bioavailability and clearance of midazolam in healthy individuals without obesity. METHODS: This study included 33 healthy volunteers [28 ± 8 years, 21% males, body mass index (BMI) 23 ± 2.5 kg/m(2)] subjected to four pharmacokinetic investigations over a 2-month period (weeks 0, 2, 4, and 8). Semi-simultaneous oral (0 h) and intravenous (2 h later) midazolam dosing was used to assess absolute bioavailability and clearance of midazolam. RESULTS: At baseline, mean absolute bioavailability and clearance were 46 ± 18% and 31 ± 10 L/h, respectively. The mean coefficient of variation (CV, %) for absolute bioavailability and clearance of midazolam was 26 ± 15% and 20 ± 10%, respectively. Approximately one-third had a CV > 30% for absolute bioavailability, while 13% had a CV > 30% for clearance. CONCLUSIONS: On average, intraindividual variability in absolute bioavailability and clearance of midazolam was low to moderate; however, especially absolute bioavailability showed considerable variability in a relatively large proportion of the individuals. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40262-023-01257-z.
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Intraindividual Variability in Absolute Bioavailability and Clearance of Midazolam in Healthy Individuals
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Autor/in / Beteiligte Person: | Kvitne, Kine Eide ; Drevland, Ole Martin ; Haugli, Nora ; Skadberg, Eline ; Zaré, Hasse Khiabani ; Åsberg, Anders ; Robertsen, Ida |
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Zeitschrift: | Clin Pharmacokinet, 2023 |
Veröffentlichung: | Springer International Publishing, 2023 |
Medientyp: | academicJournal |
DOI: | 10.1007/s40262-023-01257-z |
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