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• W2049253858 abstract "1 The characteristics and mechanism of fluctuations in diazepam and N-desmethyldiazepam concentrations and diazepam free fraction were studied in six volunteers, who received diazepam (10 mg, i.v. over 20 min) and in five chronic diazepam users. 2 Within a day total diazepam and N-desmethyldiazepam concentrations varied significantly (P less than 0.001) and were lower than predicted between 23.00 and 08.00 h and higher by 09.00 h. In contrast, diazepam free fraction also varied significantly (P less than 0.001) and was highest between 23.00 and 08.00 h and lower by 09.00 h. Coincident increases in total diazepam concentrations (P less than 0.005) and decreases in diazepam free fraction were associated with food intake (P less than 0.05). 3 The coincident diurnal variations in diazepam and N-desmethyldiazepam concentrations and the negative correlation between total diazepam concentration and diazepam free fraction (r = 0.73, P less than 0.001) suggest that the mechanism of the fluctuations is intravascular and tissue redistribution rather than effect on drug biotransformation. 4 These variations may introduce large between and within investigator experimental differences in the determination of kinetic parameters. Free drug concentration varies over the day, and within day variations in clinical effect may be observed." @default.
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• W2049253858 date "1980-03-01" @default.
• W2049253858 modified "2023-10-17" @default.
• W2049253858 title "Diurnal variations in plasma diazepam concentrations associated with reciprocal changes in free fraction." @default.
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• W2049253858 doi "https://doi.org/10.1111/j.1365-2125.1980.tb04836.x" @default.
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