Abstract
1. In the present study possible relationships between cardiovascular and respiratory effects and plasma concentrations were investigated after administration of midazolam and diazepam. Eight healthy volunteers were given three injections at 20 min intervals of equipotent sedative doses of midazolam (0.05 mg kg-1) and diazepam (0.15 mg kg-1) in a randomized double-blind cross-over design. Blood pressure, blood-gases and respiration measured nonivasively, were monitored throughout the experimental session of 160 min, and frequent blood samples were collected during the session. 2. Correlations between the blood pressure reduction, the increase of PaCO2 in blood, and plasma concentrations were found for both drugs. A maximal reduction of blood pressure and PaCO2 was produced after sedative doses of midazolam and diazepam. 3. A possible acute tolerance development towards the blood pressure reduction was found after the repeated administration of diazepam but not after the midazolam administration. 4. The plasma concentrations producing half the maximal effects after administration of midazolam was 50-60 ng ml-1, indicating that the influence on blood pressure and PaCO2 after drug administration is evoked at lower plasma concentrations than sedation. 5. No correlation between the respiratory effects and plasma concentrations was found for either drug.
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Selected References
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- Al-Khudhairi D., Askitopoulou H., Whitwam J. G. Acute "tolerance" to the central respiratory effects of midazolam in the dog. Br J Anaesth. 1982 Sep;54(9):953–958. doi: 10.1093/bja/54.9.953. [DOI] [PubMed] [Google Scholar]
- Berggren L., Eriksson I., Mollenholt P., Sunzel M. Changes in respiratory pattern after repeated doses of diazepam and midazolam in healthy subjects. Acta Anaesthesiol Scand. 1987 Nov;31(8):667–672. doi: 10.1111/j.1399-6576.1987.tb02643.x. [DOI] [PubMed] [Google Scholar]
- Berggren L., Eriksson I., Mollenholt P., Wickbom G. Sedation for fibreoptic gastroscopy: a comparative study of midazolam and diazepam. Br J Anaesth. 1983 Apr;55(4):289–296. doi: 10.1093/bja/55.4.289. [DOI] [PubMed] [Google Scholar]
- Boxenbaum H. G., Riegelman S., Elashoff R. M. Statistical estimations in pharmacokinetics. J Pharmacokinet Biopharm. 1974 Apr;2(2):123–148. doi: 10.1007/BF01061504. [DOI] [PubMed] [Google Scholar]
- Crevoisier C., Eckert M., Heizmann P., Thurneysen D. J., Ziegler W. H. Relation entre l'effet clinique et la pharmacocinétique du midazolam après administration i.v. et i.m. 2ème communcation: Aspects pharmacocinétiques. Arzneimittelforschung. 1981;31(12A):2211–2215. [PubMed] [Google Scholar]
- Crevoisier C., Ziegler W. H., Eckert M., Heizmann P. Relationship between plasma concentration and effect of midazolam after oral and intravenous administration. Br J Clin Pharmacol. 1983;16 (Suppl 1):51S–61S. doi: 10.1111/j.1365-2125.1983.tb02271.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dasberg H. H., van der Kleijn E., Guelen J. P., van Praag H. M. Plasma concentrations of diazepam and of its metabolite N-desmethyldiazepam in relation to anxiolytic effect. Clin Pharmacol Ther. 1974 May;15(5):473–483. doi: 10.1002/cpt1974155473. [DOI] [PubMed] [Google Scholar]
- Eriksson I., Berggren L. Effects of repeated doses of benzodiazepines on arterial blood gases and transcutaneous PO2. Acta Anaesthesiol Scand. 1987 Jul;31(5):357–361. doi: 10.1111/j.1399-6576.1987.tb02584.x. [DOI] [PubMed] [Google Scholar]
- Eriksson I., Berggren L., Hallgren S. CO2 production and breathing pattern during invasive and non-invasive respiratory monitoring. Acta Anaesthesiol Scand. 1986 Aug;30(6):438–443. doi: 10.1111/j.1399-6576.1986.tb02448.x. [DOI] [PubMed] [Google Scholar]
- Gamble J. A., Kawar P., Dundee J. W., Moore J., Briggs L. P. Evaluation of midazolam as an intravenous induction agent. Anaesthesia. 1981 Sep;36(9):868–873. doi: 10.1111/j.1365-2044.1981.tb08859.x. [DOI] [PubMed] [Google Scholar]
- Hamdy N. A., Kennedy H. J., Nicholl J., Triger D. R. Sedation for gastroscopy: a comparative study of midazolam and Diazemuls in patients with and without cirrhosis. Br J Clin Pharmacol. 1986 Dec;22(6):643–647. doi: 10.1111/j.1365-2125.1986.tb02952.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holford N. H., Sheiner L. B. Understanding the dose-effect relationship: clinical application of pharmacokinetic-pharmacodynamic models. Clin Pharmacokinet. 1981 Nov-Dec;6(6):429–453. doi: 10.2165/00003088-198106060-00002. [DOI] [PubMed] [Google Scholar]
- Jack M. L., Colburn W. A. Pharmacokinetic model for diazepam and its major metabolite desmethyldiazepam following diazepam administration. J Pharm Sci. 1983 Nov;72(11):1318–1323. doi: 10.1002/jps.2600721120. [DOI] [PubMed] [Google Scholar]
- Kaplan S. A., Jack M. L., Alexander K., Weinfeld R. E. Pharmacokinetic profile of diazepam in man following single intravenous and oral and chronic oral administrations. J Pharm Sci. 1973 Nov;62(11):1789–1796. doi: 10.1002/jps.2600621111. [DOI] [PubMed] [Google Scholar]
- Lebowitz P. W., Cote M. E., Daniels A. L., Martyn J. A., Teplick R. S., Davison J. K., Sunder N. Cardiovascular effects of midazolam and thiopentone for induction of anaesthesia in ill surgical patients. Can Anaesth Soc J. 1983 Jan;30(1):19–23. doi: 10.1007/BF03007711. [DOI] [PubMed] [Google Scholar]
- Lebowitz P. W., Cote M. E., Daniels A. L., Ramsey F. M., Martyn J. A., Teplick R. S., Davison J. K. Comparative cardiovascular effects of midazolam and thiopental in healthy patients. Anesth Analg. 1982 Sep;61(9):771–775. [PubMed] [Google Scholar]
- Marty J., Gauzit R., Lefevre P., Couderc E., Farinotti R., Henzel C., Desmonts J. M. Effects of diazepam and midazolam on baroreflex control of heart rate and on sympathetic activity in humans. Anesth Analg. 1986 Feb;65(2):113–119. [PubMed] [Google Scholar]
- Marty J., Nitenberg A., Blanchet F., Zouioueche S., Desmonts J. M. Effects of midazolam on the coronary circulation in patients with coronary artery disease. Anesthesiology. 1986 Feb;64(2):206–210. doi: 10.1097/00000542-198602000-00013. [DOI] [PubMed] [Google Scholar]
- Milic-Emili J. Recent advances in the evaluation of respiratory drive. Int Anesthesiol Clin. 1977 Summer;15(2):39–58. doi: 10.1097/00004311-197715020-00002. [DOI] [PubMed] [Google Scholar]
- Reves J. G., Fragen R. J., Vinik H. R., Greenblatt D. J. Midazolam: pharmacology and uses. Anesthesiology. 1985 Mar;62(3):310–324. [PubMed] [Google Scholar]
- Rutherford D. M. Rapid micro-method for the measurement of diazepam and desmethyldiazepam in blood plasma by gas-liquid chromatography. J Chromatogr. 1977 Jul 21;137(2):439–448. doi: 10.1016/s0021-9673(00)81366-7. [DOI] [PubMed] [Google Scholar]
- Yamaoka K., Nakagawa T., Uno T. Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations. J Pharmacokinet Biopharm. 1978 Apr;6(2):165–175. doi: 10.1007/BF01117450. [DOI] [PubMed] [Google Scholar]
