RESUMO
In a double-blind crossover study, the pharmacokinetics and effects on night-time respiration and body movements of midazolam 7.5 mg, flunitrazepam 1 mg, and placebo were studied in 5 elderly insomniac patients with the static charge sensitive bed-method (SCSB). In a supine position, the gastrointestinal absorption rate of flunitrazepam (tmax 0.6 h) was faster than that of midazolam (tmax 0.95 h). The elimination phase half-life of midazolam was about twice as long as reported earlier in healthy adult volunteers, but ageing did not affect the elimination of flunitrazepam. The shape of the serum concentration-time curve of both benzodiazepine derivatives was quite similar. The sleep of these five insomniacs became more peaceful and the respiration more regular during midazolam and flunitrazepam, compared with placebo. Both benzodiazepines significantly decreased body movements and the cumulative movement time remained shorter throughout the night, compared with placebo. Total variability (VI) was clearly decreased with flurazepam, and a similar but not statistically significant tendency was seen with midazolam, compared with placebo. Accordingly, the proportion of quiet sleep (QS) increased (p = 0.014) and the proportion of active sleep (AS) decreased (p = 0.019) with both benzodiazepines, compared with placebo. This reflects the changed control of respiration by higher brain structures. No signs of increased respiratory resistance (i.e. ballistocardiographic respiratory amplitude variation BRV < 60%) were seen with either of the drugs or placebo. There were no differences in the subjects' own estimation of their sleep during medication with these drugs. Only the sleep onset latency was shorter with flunitrazepam compared with midazolam and placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
