Lack of effect of nitrendipine on the pharmacokinetics and pharmacodynamics of midazolam during steady state.

Abstract

and lInstitute of Psychosomatic Research, Herbsthalde 11, 7000 Stuttgart 1 FRG 1 The possible interaction (as indicated by rat experiments) between calcium channel blocking agents and benzodiazepines has been evaluated in nine healthy subjects. 2 Subsequently to an intravenous loading dose (0.07 mg kg-1) midazolam was infused for 6 h (0.035 mg kg-' h-1) and steady state plasma levels between 54 to 114 ,ug 1-1 were achieved. Two hours after the bolus of midazolam a solution of 20 mg nitrendipine or placebo was administered in a randomized, double-blind crossover fashion. 3 The marked sedative-hypnotic effects of midazolam as assessed by visual analogue scales (about four fold increase in the sedation index) and choice reaction time (100% prolongation) indicated some form of adaptation or tolerance towards the end of the infusion. However, the midazolam-induced impairments were not affected by nitrendipine. 4 EEG-data indicated stabile benzodiazepine-like effects during the complete infusion period of midazolam (e.g. decrease in alpha activity, increase in sigma, delta 2 and beta 1 activity). Again, these alterations were not modified by nitrendipine. 5 There was also no pharmacokinetic interaction between both agents, since elimination of midazolam (t½ -2.5 ± 0.8 h; CL -548 ± 143 ml min-') was in close agreement with control values (t½ = 2.4 ± 0.6 h; CL = 512 ± 102 ml min-'). Likewise, plasma levels of nitrendipine were comparable to literature data. 6 Thus, it could be concluded that nitrendipine does not affect the action of midazolam and therefore a direct involvement of calcium at the benzodiazepine receptor site is unlikely under our clinical conditions.

Possible interaction of fluoroquinolones with the benzodiazepine‐GABAA‐ receptor complex.

“…This pattern was known from different studies conducted with midazolam (Handel et al, 1988;Klotz et al, 1985), as well as other BZD (Sittig et al, 1982). Additionally, the increased sedation index and reported side effects such as fatigue and amnesia, indicate the typical agonist BZD action.…”

Feasibility of Anesthesia Induction by a Combination of Topical Pharyngeal Using Lidocaine Spray and Moderate Intravenous Sedation in a Flexible Bronchoscopic Procedure

“…In addition, objective evaluation such as number of cough and subjective evaluation such as the ease of performing the examination by the bron-choscopist would be also important to assess feasibility. Although patients' full recovery from sedation was not defined in this study, one study reported that half-life of midazolam is about 2.5 h 22) . Therefore, most of the patients were considered to have recovered almost completely enough to reply to questionnaires.…”

Relationship between low midazolam metabolism by cytochrome P450 3A in mice and the high incidence of birth defects

“…Benzodiazepines are reported to confer a high risk of teratogenic effects in foetuses when used during pregnancy (Wikner et al, 2007). These drugs are known to have a short half-life of 2 hr in human adults and are easily eliminated from the body (Eberts et al, 1981;Klotz et al, 1985;Handel et al, 1988). Specifically, they are rapidly metabolized into the 1'-OH or 4'-OH form, primarily by CYP3A4 in the human liver or CYP3A11 in the mouse liver (Kronbach et al, 1989;Thummel and Wilkinson, 1998;Hyland et al, 2009).…”