The Experts below are selected from a list of 144 Experts worldwide ranked by ideXlab platform
Koichi Otani - One of the best experts on this subject based on the ideXlab platform.
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Rifampicin markedly decreases plasma concentration and hypnotic effect of Brotizolam.
Therapeutic drug monitoring, 2006Co-Authors: Yukihiro Ujiie, Takashi Fukasawa, Akihito Suzuki, Tomonori Tateishi, Norio Yasui-furukori, Koichi OtaniAbstract:The purpose of the present study was to examine the effects of rifampicin on the single oral dose pharmacokinetics and pharmacodynamics of Brotizolam. Thirteen healthy male volunteers received rifampicin 450mg/day, or matched placebo, for 7 days in a double-blind randomized crossover manner. On the sixth day they received a single oral 0.5-mg dose of Brotizolam, and blood sampling was performed for 24 hours, together with an assessment of psychomotor function using the Digit Symbol Substitution Test and the Stanford Sleepiness Scale. Rifampicin treatment significantly (P < 0.001) decreased the peak plasma concentration (69%), total area under the plasma concentration-time curve (90%) and elimination half-life (79%) of Brotizolam. Rifampicin significantly increased the area under the score-time curve of the Digit Symbol Substitution Test (P < 0.01), and decreased that of the Stanford Sleepiness Scale (P < 0.05). The present study suggests that rifampicin markedly decreases plasma concentration and hypnotic effect of Brotizolam and, therefore, this combination is not recommended in clinical practice.
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inhibition of the metabolism of Brotizolam by erythromycin in humans in vivo evidence for the involvement of cyp3a4 in Brotizolam metabolism
British Journal of Clinical Pharmacology, 2005Co-Authors: Takaki Tokairin, Takashi Fukasawa, Norio Yasuifurukori, Toshiaki Aoshima, Akihito Suzuki, Yoshimasa Inoue, Tomonori Tateishi, Koichi OtaniAbstract:Aims To obtain in vivo evidence for the involvement of cytochrome P450 (CYP) 3A4 in the metabolism of Brotizolam. Methods Fourteen healthy male volunteers received erythromycin 1200 mg day−1 or placebo for 7 days in a double-blind randomized crossover manner. On the 6th day they received a single oral 0.5-mg dose of Brotizolam, and blood samplings were performed for 24 h. Results Erythromycin treatment significantly increased the peak plasma concentration (P < 0.05), total area under the plasma concentration-time curve (P < 0.01), and elimination half-life (P < 0.01) of Brotizolam. Conclusions The present study provides in vivo evidence for the involvement of CYP3A4 in Brotizolam metabolism.
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Inhibition of the metabolism of Brotizolam by erythromycin in humans: in vivo evidence for the involvement of CYP3A4 in Brotizolam metabolism
British journal of clinical pharmacology, 2005Co-Authors: Takaki Tokairin, Takashi Fukasawa, Toshiaki Aoshima, Akihito Suzuki, Yoshimasa Inoue, Tomonori Tateishi, Norio Yasui-furukori, Koichi OtaniAbstract:Aims To obtain in vivo evidence for the involvement of cytochrome P450 (CYP) 3A4 in the metabolism of Brotizolam. Methods Fourteen healthy male volunteers received erythromycin 1200 mg day−1 or placebo for 7 days in a double-blind randomized crossover manner. On the 6th day they received a single oral 0.5-mg dose of Brotizolam, and blood samplings were performed for 24 h. Results Erythromycin treatment significantly increased the peak plasma concentration (P
Sunao Kaneko - One of the best experts on this subject based on the ideXlab platform.
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effect of itraconazole on the pharmacokinetics and pharmacodynamics of a single oral dose of Brotizolam
British Journal of Clinical Pharmacology, 2004Co-Authors: Takako Osanai, Tadashi Ohkubo, Norio Yasui, T Kondo, Sunao KanekoAbstract:Aims To assess the effect of itraconazole, a potent inhibitor of cytochrome P450 (CYP)3A4, on the single oral dose pharmacokinetics and pharmacodynamics of Brotizolam. Methods In this randomized, double-blind, cross-over trial 10 healthy male subjects received either itraconazole 200 mg or matched placebo once daily for 4 days. On day 4, a single 0.5 mg dose of Brotizolam was administered orally. Plasma concentrations of Brotizolam were followed up to 24 h, together with assessment of psychomotor function measured by the digit symbol substitution test (DSST), visual analogue scales and UKU side-effect rating scale. Results Itraconazole significantly (P < 0.001) decreased the apparent oral clearance (CL/F) (16.47 ± 4.3 vs 3.91 ± 2.1), increased the area under the concentration-time curves (AUC) from 0 h to 24 h (28.37 ± 10.8 vs 68.71 ± 24.1 ng ml h−1), and prolonged the elimination half-life (4.56 ± 1.4 vs 23.27 ± 10.3 h) of Brotizolam. The AUC(0,24 h) of the DSST (P < 0.001) and the item ‘sleepiness’ of UKU (P < 0.05) were significantly decreased. Conclusions Itraconazole increases plasma concentrations of Brotizolam probably via its inhibitory effect on CYP3A4 Brotizolam metabolism.
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Effect of itraconazole on the pharmacokinetics and pharmacodynamics of a single oral dose of Brotizolam
British journal of clinical pharmacology, 2004Co-Authors: Takako Osanai, Tadashi Ohkubo, Norio Yasui, T Kondo, Sunao KanekoAbstract:Aims To assess the effect of itraconazole, a potent inhibitor of cytochrome P450 (CYP)3A4, on the single oral dose pharmacokinetics and pharmacodynamics of Brotizolam. Methods In this randomized, double-blind, cross-over trial 10 healthy male subjects received either itraconazole 200 mg or matched placebo once daily for 4 days. On day 4, a single 0.5 mg dose of Brotizolam was administered orally. Plasma concentrations of Brotizolam were followed up to 24 h, together with assessment of psychomotor function measured by the digit symbol substitution test (DSST), visual analogue scales and UKU side-effect rating scale. Results Itraconazole significantly (P
Takako Osanai - One of the best experts on this subject based on the ideXlab platform.
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effect of itraconazole on the pharmacokinetics and pharmacodynamics of a single oral dose of Brotizolam
British Journal of Clinical Pharmacology, 2004Co-Authors: Takako Osanai, Tadashi Ohkubo, Norio Yasui, T Kondo, Sunao KanekoAbstract:Aims To assess the effect of itraconazole, a potent inhibitor of cytochrome P450 (CYP)3A4, on the single oral dose pharmacokinetics and pharmacodynamics of Brotizolam. Methods In this randomized, double-blind, cross-over trial 10 healthy male subjects received either itraconazole 200 mg or matched placebo once daily for 4 days. On day 4, a single 0.5 mg dose of Brotizolam was administered orally. Plasma concentrations of Brotizolam were followed up to 24 h, together with assessment of psychomotor function measured by the digit symbol substitution test (DSST), visual analogue scales and UKU side-effect rating scale. Results Itraconazole significantly (P < 0.001) decreased the apparent oral clearance (CL/F) (16.47 ± 4.3 vs 3.91 ± 2.1), increased the area under the concentration-time curves (AUC) from 0 h to 24 h (28.37 ± 10.8 vs 68.71 ± 24.1 ng ml h−1), and prolonged the elimination half-life (4.56 ± 1.4 vs 23.27 ± 10.3 h) of Brotizolam. The AUC(0,24 h) of the DSST (P < 0.001) and the item ‘sleepiness’ of UKU (P < 0.05) were significantly decreased. Conclusions Itraconazole increases plasma concentrations of Brotizolam probably via its inhibitory effect on CYP3A4 Brotizolam metabolism.
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Effect of itraconazole on the pharmacokinetics and pharmacodynamics of a single oral dose of Brotizolam
British journal of clinical pharmacology, 2004Co-Authors: Takako Osanai, Tadashi Ohkubo, Norio Yasui, T Kondo, Sunao KanekoAbstract:Aims To assess the effect of itraconazole, a potent inhibitor of cytochrome P450 (CYP)3A4, on the single oral dose pharmacokinetics and pharmacodynamics of Brotizolam. Methods In this randomized, double-blind, cross-over trial 10 healthy male subjects received either itraconazole 200 mg or matched placebo once daily for 4 days. On day 4, a single 0.5 mg dose of Brotizolam was administered orally. Plasma concentrations of Brotizolam were followed up to 24 h, together with assessment of psychomotor function measured by the digit symbol substitution test (DSST), visual analogue scales and UKU side-effect rating scale. Results Itraconazole significantly (P
William L. Woolverton - One of the best experts on this subject based on the ideXlab platform.
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Discriminative and reinforcing effects of Brotizolam in rhesus monkeys
Psychopharmacology, 1991Co-Authors: Michael A. Nader, Gail Winger, James H. Woods, William L. WoolvertonAbstract:The reinforcing and discriminative stimulus effects of Brotizolam, a benzodiazepine-hypnotic, were evaluated in rhesus monkeys. In one experiment, separate groups of monkeys ( N =3/group) were trained to discriminate pentobarbital (10 mg/kg, IG) or d -amphetamine (0.56–1.0 mg/kg, IG) from saline, in a discrete-trials avoidance/escape paradigm. Pentobarbital (5.6–10 mg/kg), diazepam (1.0–1.7 mg/kg), and Brotizolam (0.3–1.7 mg/kg) resulted in 100% drug-lever responding in all three pentobarbital-trained monkeys. In d -amphetamine-trained monkeys Brotizolam administration resulted only in saline-lever responding. In another experiment, monkeys were surgically prepared with indwelling intravenous catheters and lever pressing resulted in an injection of 0.1 mg/kg/injection sodium methohexital under a fixed-ratio 10 (FR 10) schedule. Pentobarbital (0.01–0.3 mg/kg/injection) and diazepam (0.003–0.10 mg/kg/injection) maintained responding above saline control levels when substituted for methohexital. Brotizolam (0.001–0.01 mg/kg/injection) resulted in more injections received compared to saline, but fewer injections compared to pentobarbital or diazepam. Thus, results from the present experiment suggest that Brotizolam would have pentobarbital-like subjective effects. However, the abuse liability of Brotizolam may be lower than that for diazepam.
Shigenobu Shibata - One of the best experts on this subject based on the ideXlab platform.
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inhibitory action of Brotizolam on circadian and light induced per1 and per2 expression in the hamster suprachiasmatic nucleus
British Journal of Pharmacology, 2000Co-Authors: Shin Ichi Yokota, Kazumasa Horikawa, Masashi Akiyama, Takahiro Moriya, Shizufumi Ebihara, Goyo Komuro, Tatsuro Ohta, Shigenobu ShibataAbstract:Triazolam reportedly causes phase advances in hamster wheel-running rhythm after injection during subjective daytime. However, it is unclear whether benzodiazepine affects the PER: gene expression accompanying a behavioural phase shift. Brotizolam (0.5 - 10 mg kg(-1)) induced large phase advances in hamster rhythm when injected during mid-subjective daytime (circadian time 6 or 9), but not at circadian time 0, 3 or 15. Brotizolam (5 mg kg(-1)) significantly reduced the expression of PER:1 and PER:2 in the suprachiasmatic nucleus 1 and 2 h after injection at circadian time 6, and slightly reduced them at circadian time 20. Injection of 8-OH-DPAT (5 mg kg(-1)) at subjective daytime induced similar phase advances with a reduction of PER:1 and PER:2 expression. Co-administration of Brotizolam with 8-OH DPAT failed to potentiate the 8-OH DPAT-induced phase advances and reduced PER: expression. Both phase advance and rapid induction of PER:1 and PER:2 in the suprachiasmatic nucleus after light exposure (5 lux, 15 min) at circadian time 20 was strongly attenuated by co-treatment with Brotizolam 5 mg kg(-1). The present results strongly suggest that reduction of PER:1 and/or PER:2 expression during subjective daytime by Brotizolam may be an important step in causing a behavioural phase advance. The co-administration experiment suggests that common mechanism(s) are involved in Brotizolam- or 8-OH DPAT-induced phase advances and the reduction of PER: gene expression. These results suggest that Brotizolam is not only a good drug for insomnia but also a drug capable of facilitating re-entrainment like melatonin.
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Inhibitory action of Brotizolam on circadian and light‐induced Per1 and Per2 expression in the hamster suprachiasmatic nucleus
British journal of pharmacology, 2000Co-Authors: Shin Ichi Yokota, Kazumasa Horikawa, Masashi Akiyama, Takahiro Moriya, Shizufumi Ebihara, Goyo Komuro, Tatsuro Ohta, Shigenobu ShibataAbstract:Triazolam reportedly causes phase advances in hamster wheel-running rhythm after injection during subjective daytime. However, it is unclear whether benzodiazepine affects the PER: gene expression accompanying a behavioural phase shift. Brotizolam (0.5 - 10 mg kg(-1)) induced large phase advances in hamster rhythm when injected during mid-subjective daytime (circadian time 6 or 9), but not at circadian time 0, 3 or 15. Brotizolam (5 mg kg(-1)) significantly reduced the expression of PER:1 and PER:2 in the suprachiasmatic nucleus 1 and 2 h after injection at circadian time 6, and slightly reduced them at circadian time 20. Injection of 8-OH-DPAT (5 mg kg(-1)) at subjective daytime induced similar phase advances with a reduction of PER:1 and PER:2 expression. Co-administration of Brotizolam with 8-OH DPAT failed to potentiate the 8-OH DPAT-induced phase advances and reduced PER: expression. Both phase advance and rapid induction of PER:1 and PER:2 in the suprachiasmatic nucleus after light exposure (5 lux, 15 min) at circadian time 20 was strongly attenuated by co-treatment with Brotizolam 5 mg kg(-1). The present results strongly suggest that reduction of PER:1 and/or PER:2 expression during subjective daytime by Brotizolam may be an important step in causing a behavioural phase advance. The co-administration experiment suggests that common mechanism(s) are involved in Brotizolam- or 8-OH DPAT-induced phase advances and the reduction of PER: gene expression. These results suggest that Brotizolam is not only a good drug for insomnia but also a drug capable of facilitating re-entrainment like melatonin.
