Automated Gas Chromatography for Studies of Midazolam Pharmacokinetics

Greenblatt, David J.; Locniskar, Ann; Ochs, Hermann R.; Lauven, P. M.

doi:10.1097/00000542-198108000-00014

Cited by 87 publications

(17 citation statements)

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“…The plasma concentrations of midazolam, ahydroxymidazolam and a-hydroxymidazolam glucuronide in patients 2, 3, 4, 5 and 6 during the anhepatic period and following reperfusion are shown in Figure 1 (Mahon et al, 1977)), the kidney (which has been implicated in the metabolism of morphine (Moore etal., 1986)), and the lung (Heizman et al, 1983 (Brown et al, 1979;Dundee et al, 1980Dundee et al, , 1986Greenblatt et al, 1981 and. The duration of the anhepatic period is necessarily short and the calculated half-life may therefore represent a distribution rather than an elimination half-life. Caution in the application of these results to patients with severe liver failure is necessary.…”

Section: Resultsmentioning

confidence: 99%

Extra‐hepatic metabolism of midazolam.

Manara

Dawling

1989

Brit J Clinical Pharma

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Six patients received 10 mg of midazolam intravenously during the anhepatic period of liver transplantation. Arterial blood was sampled during this time and for a similar period following revascularisation. The plasma was analysed using gas chromatography and electron capture detection (GC-ECD) for midazolam a-hydroxymidazolam and ahydroxymidazolam glucuronide. Five of the six patients had small but significant concentrations of metabolites detected during the anhepatic period, demonstrating the presence of extra-hepatic sites of metabolism for this drug. The remaining patient had plasma concentrations of metabolites below the lower limit of detection (2,ug 1-1). This may represent a pharmacogenetic abnormality or a temporary failure of midazolam metabolism secondary to the patients illness affecting the extra-hepatic sites of metabolism.

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Section: Resultsmentioning

confidence: 99%

Extra‐hepatic metabolism of midazolam.

Manara

Dawling

1989

Brit J Clinical Pharma

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“…Hypnotics with a long elimination half-life (i.e. flunitrazepam and flurazepam) induced a long-lasting reduction of motor activity, whereas compounds with a short half-life (triazolam and midazolam; see Breimer & Jochemsen, 1981;Greenblatt et al, 1981) had only a short-lasting effect. Dettli (1983) has recently pointed out that the elimination halflife cannot be regarded as a valid classification criterion for separating long-acting and shortacting hypnotics, since the duration of action may be influenced also by several other parameters (e.g.…”

Section: Methodsmentioning

confidence: 99%

Ambulatory motor activity monitoring to study the timecourse of hypnotic action.

Borbély¹

1984

Brit J Clinical Pharma

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“…with an ultrashort elimination half-life of 2-3 h [5][6][7], Data arc lacking regarding the effective ness of midazolam for inducing and main taining sleep and the side effects of the drug, including the presence of any side effects fol lowing withdrawal. Benzodiazepines with either short or long elimination half-lives have potential advantages and disadvantages when used in the adjunctive treatment of insomnia [8], Although benzodiazepine hyp notic drugs with short elimination half-lives may cause less impairment of daytime per formance [9], they have a greater potential fora rapid development of tolerance [10.…”

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confidence: 99%

Midazolam: Dose-Response Studies of Effectiveness and Rebound Insomnia

et al. 1983

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Midazolam, an investigational hypnotic, was evaluated for effectiveness, side effects, and withdrawal phenomena in doses of 10, 20, and 30 mg in three separate sleep laboratory studies, each including 4 placebo-baseline nights, 7 drug nights, and 3 placebo-withdrawal nights. Only a slight to moderate degree of effectiveness was shown across the three doses; this effectiveness was much more pronounced during the first third of the night. There was no dose-response effect for effectiveness with either initial or continued drug administration. In general, there was less effectiveness on the last 3 drug nights, indicating a potential for the development of tolerance over a relatively short period of time. Following withdrawal there was a marked dose-related worsening of sleep above baseline levels (rebound insomnia).

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Automated Gas Chromatography for Studies of Midazolam Pharmacokinetics

Cited by 87 publications

References 0 publications

Extra‐hepatic metabolism of midazolam.

Extra‐hepatic metabolism of midazolam.

Ambulatory motor activity monitoring to study the timecourse of hypnotic action.

Midazolam: Dose-Response Studies of Effectiveness and Rebound Insomnia

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