CAN:s bibliotek

*000      am
*00118596
*008070120|1989|||||||||||e|m||||||||0|eng|d
*020  $a91-554-2478-3$x91-554-2478-3
*1001 $aSunzel, Maria
*24510$aPotential time dependencies in the pharmacokinetics and pharmacodynamics of the benzodiazepine midazolam.
*260  $aUppsala,$c1989$y1989
*300  $a40 s :$bill.
*440 0$aComprehensive summaries of Uppsala dissertations from the Faculty of Pharmacy ;$v57
*500  $aHärtill 5 uppsatser
*520  $aThe influence of different rates of intravenous administration on the pharmacodynamics of midazolam was studied in the rat and man. The pharmacokinetics of the drug was determined in the rat. The disposition of midazolam in the rat was characterized by extensive distribution, and a flow-dependent total plasma clearance of the drug. A reduced locomotor activity was observed in rats receiving a constant intravenous infusion of midazolam during seven days. No tolerance development towards the pharmacological actions of midazolam could be discerned during the drug administration. When drug infusion was discontinued, the locomotor activity in rats receiving midazolam was restored to that of the control group within two days. Different rates of intravenous injection of midazolam in sedative doses administered to aged male patients produced a marked respiratory depression when given over a shorter time period than 40 seconds. Relationships between plasma levels of midazolam and respiratory and cardiovascular effects were observed in man. There was a short delay of the onset of the effects indicating a disequilibrium between the plasma and effect site concentrations of midazolam during the first minutes after drug administration. No time-dependent changes in the pharmacodynamics of midazolam was observed. However, after diazepam administration in equipotent doses to those of midazolam, possible acute tolerance development to the blood pressure reduction was observed.
*650 4$aMidazolam
*650 4$aAnimal
*650 4$aRats
*650 4$aBenzodiazepines
*650 4$aPharmacokinetics
*650 4$aInjections, intravenous
*650 4$aMale
*653  $aBensodiazepiner
*653  $aDjurförsök
*653  $aMän
*852  $hDiss.135
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