Midazolam: kinetics and effects on memory, sensorium, and haemodynamics.

Abstract

1 This study aimed not only to compare the pharmacokinetics of oral and intravenous doses of the new water-soluble benzodiazepine, midazolam, but also to study the effects on haemodynamics, sensorium, and memory performance. 2 Eight normal human volunteers each received a single 15 mg dose of midazolam base orally and intravenously in randomized sequence 2 weeks apart. Serial venous samples were obtained for 12 h after dosing. Vital signs, sensorium testing and memory testing using word lists were also performed. Computerized non-linear least squares curve-fitting of the two-compartment open model to the oral and intravenous data simultaneously yielded the following estimates: VI, 0.331 kg-1, Vdss, 1.081 kg-1, t2,x, 0.10 h, t½2,z, 1.89 h, ka 1.17 h-1 and bioavailability, 49%. The intravenous dose decreased the systolic pressure 22 mm Hg during the first half-hour and the oral dose had 50% less effect. Most subjects became drowsy halfway through the infusion and were only rousable to voice by its end. The sensorium was clear by 2-3 h. After oral dosing the peak sensorium effects of ataxiadysarthria were seen at 30 min and had cleared by 2 h. Memory testing showed that memory acquisition was markedly impaired for at least 90 min after the intravenous dose and slight recovery was apparent at this time after the oral dose. Memory performance was proportionately more impaired than the sensorium score. 3 We conclude that: (a) midazolam kinetics are characterized by rapid absorption, but incomplete bioavailability and rapid elimination, (b) midazolam intravenously may lower blood pressure significantly, and (c) the level of consciousness correlates poorly with the degree of memory impairment.

The differential effects of flumazenil on the psychomotor and amnesic actions of midazolam

“…Compared with their performance at baseline, patients were severely impaired after midazolam on free recall, as has been found previously (Langlois et al, 1987). This impairment was more pronounced on delayed recall than on immediate recall as has been reported in many previous studies of benzodiazepines (Curran, 1986).…”

Pharmacokinetics and preliminary observations of behavioral changes following administration of midazolam to dogs

“…Systemic elimination of midazolam is more rapid in dogs than in man. Reported values for mean tIhp and Cl in man range from 1.9-2.5 h and 6.7-10.8 ml/min/kg, respectively (Greenblatt et al, 1981;Greenblatt et al, 1984;Langlois et al, 1987;Ochs, Greenblatt & Knuchel, 1985;Puglisi et al, 1978;Smith et al, 198 1). This is not surprising considering dogs are able to metabolize other benzodiazepines much more rapidly than man (Klotz, Antonin & Bieck, 1976;Ochs et al, 1988).…”

Sedação consciente endovenosa com midazolam no tratamento odontológico de pessoas com deficiência

“…Mas, dentre elas, o grupo dos benzodiazepínicos vem se destacando para este fim. E, dentro deste grupo, o midazolam tem demonstrado maior eficácia e segurança 16,18,19,26 . Suas características farmacológicas, tais como: início de ação rápida, meia vida curta, duração da sedação adequada, bons efeitos ansiolíticos, hipnóticos e amnésicos, baixo custo e existência de medicamento antagonista específico (flumazenil) estão entre os objetivos principais para a escolha desta droga.…”