Midazolam kinetics

Allonen, H; Ziegler, G.; Klotz, Ulrich

doi:10.1038/clpt.1981.217

Cited by 303 publications

(166 citation statements)

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“…Such plasma drug concentration-effect relationships have been described previously in healthy volunteers (Allonen et al, 1981) as well as in surgical patients (Persson et al, 1988). Likewise, the sedative effects were of short duration confirming the findings of others (Allonen et al, 1981;Dundee et al, 1984;Kanto, 1985;Kassai et al, 1988;Klotz & Ziegler, 1982;Persson etal., 1988;Reves et al, 1985). Hence the pharmacokinetic and pharmacodynamic measurements both suggest that the dosage of midazolam needs no adjustment when it is administered to patients receiving treatment with cyclosporin A.…”

Section: Discussionsupporting

confidence: 78%

“…Midazolam appears, Allonen et al (1981); Klotz & Ziegler (1982); Kanto (1985); Reves et al (1985); Dundee et al (1984); Kassai et al (1988); Persson et al (1988). KS-v vided) upon addition of cyclosporin A to liver microsomes obtained from phenobarbitoneinduced male rats (Augustine & Zemaitis, 1986).…”

Section: Discussionmentioning

confidence: 99%

“…All individuals received a single intravenous (Allonen et al, 1981;Klotz & Ziegler, 1982). The sedative-hypnotic effect of midazolam was estimated using five visual analogue scales (length each 10 cm, maximal sedative score 50 cm) where the subjects had to rate their subjective state of vigilance (e.g.…”

Section: Spectrophotometric Analysis Of Microsomal Cytochrome P-450mentioning

confidence: 99%

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Is cyclosporin A an inhibitor of drug metabolism?

Treiber

Meinshausen

et al. 1990

Brit J Clinical Pharma

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1 The potential for a drug interaction between cyclosporin A and midazolam was investigated since both compounds appear to be metabolized by the same cytochrome P-450 isoenzyme. 4 The pharmacokinetics of a single intravenous dose of midazolam (0.075 mg kg-') was studied in nine patients receiving cyclosporin A to prevent rejection of their transplanted kidneys. The average steady state blood concentrations of cyclosporin A, measured by r.i.a. using a specific monoclonal antibody, varied during a dosing interval between 175 and 600 ng ml-'.5 In these patients the hepatic elimination of midazolam was characterized by a mean t½, (± s.d.) of 2.3 ± 1.2 h and a plasma clearance (CL) of 414 ± 95 ml min-'. These values were not different from those of normal human subjects (t,, = 1.5 to 4 h, CL = 350 to 700 ml min-').6 From the results of the in vitro experiments it is concluded that cyclosporin A may potentially inhibit drug metabolism. However, therapeutic blood concentrations in vivo do not appear to be sufficient to result in an effective impairment of the hepatic elimination of midazolam when given concomitantly.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Spectrophotometric Analysis Of Microsomal Cytochrome P-450mentioning

confidence: 99%

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Is cyclosporin A an inhibitor of drug metabolism?

Treiber

Meinshausen

et al. 1990

Brit J Clinical Pharma

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“…It has an extensive first-pass metabolism mediated by a hepatic cytochrome P-450 IIIA enzyme and its oral bioavailability is less than 50% [3,4]. During treatment with erythromycin 500 mg three times daily the area under the midazolam concentration-time curve is increased more than fourfold and peak midazolam concentration almost threefold, which leads to profound and prolonged sedation [5].…”

Section: Introductionmentioning

confidence: 99%

Dose of midazolam should be reduced during diltiazem and verapamil treatments.

Backman

Olkkola

Aranko

et al. 1994

Brit J Clinical Pharma

167

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1. The effects of diltiazem and verapamil on the pharmacokinetics and pharmacodynamics of midazolam were investigated in a double‐blind randomized cross‐over study of three phases. 2. Nine healthy volunteers were given orally diltiazem (60 mg), verapamil (80 mg) or placebo three times daily for 2 days. On the second day they received a 15 mg oral dose of midazolam, after which plasma samples were collected and performance tests carried out for 17 h. 3. The area under the midazolam concentration‐time curve was increased from 12 +/‐ 1 microgram ml‐1 min to 45 +/‐ 5 micrograms ml‐1 min by diltiazem (P < 0.001) and to 35 +/‐ 5 micrograms ml‐1 min by verapamil (P < 0.001). The peak midazolam concentration was doubled (P < 0.01) and the elimination half‐life of midazolam prolonged (P < 0.05) by both diltiazem and verapamil treatments. 4. These changes in the pharmacokinetics of midazolam were also associated with profound and prolonged sedative effects. 5. If the administration of midazolam cannot be avoided, the dose of midazolam should be reduced during concomitant treatment with diltiazem and verapamil.

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“…We therefore further investigated the interaction of ciprofloxacin, norfloxacin and ofloxacin with the benzodiazepine (BZD)-GABAAreceptor complex in a radio-receptor assay (RRA) either the short-acting BZD-agonist midazolam (Allonen et al, 1981) or the specific BZDantagonist flumazenil (Klotz & Kanto, 1988 Subjects/Study design After obtaining written informed consent, 12 drug-free healthy volunteers (three females, nine males) between 23 and 47 years old participated in the study, which was approved by the Ethics committee of our hospital. Inclusion criteria were normal values in the haematological, physical and clinical safety checkups and a stable alpha-rhythm with an alpha proportion > 40%, evaluated in an EEG pre-screening.…”

Section: Introductionmentioning

confidence: 99%