Pharmacokinetics and the pharmacodynamic action of midazolam in young and elderly patients undergoing tooth extraction

Clinical Pharmacology and Therapeutics
H P PlattenU Klotz

Abstract

To determine whether age-dependent pharmacokinetic and pharmacodynamic alterations account for a more pronounced response to benzodiazepines among elderly patients. Twelve young patients and 10 elderly patients received an intravenous dose of 0.05 or 0.03 mg/kg midazolan, respectively, before third molar extraction. Postoperative pain was treated with 30 mg dihydrocodeine. Serum concentrations of midazolam and sedative effects were monitored with visual analog scales and choice reaction time measurements for 6 hours. Test values above baseline were integrated, and pharmacokinetic-pharmacodynamic analysis was performed. Heart rate, blood pressure, arterial oxygen saturation, and amnesia also were assessed. There were no significant age-dependent differences in disposition of midazolam between young and elderly patients (apparent volume of distribution, 1.3 +/- 0.2 versus 1.1 +/- 0.4 L/kg; halflife, 3.3 +/- 1.5 hours versus 3.7 +/- 2.2 hours; total body clearance, 451 +/- 186 ml/min versus 343 +/- 137 ml/min). However, higher values of area under the effect curve (AUEC) and AUEC divided by area under the serum concentration-time curve (AUC) (sensitivity index) were observed among the elderly as follows: AUEC for reaction time (AU...Continue Reading

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