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Pharmacokinetics of midazolam in critically ill pediatric patients

European Journal of Drug Metabolism and Pharmacokinetics volume 25, pages 219–221 (2000)Cite this article

Summary

Midazolam is frequently used to produce sedation in critically ill pediatric patients. We studied the pharmacokinetics of midazolam in 22 patients (age 8 days to 16 years). The intravenous infusion rate to produce sedation ranged from 49–385 mcg/kg/hr.

The blood samples were obtained at steady-state and midazolam was measured by gas chromatography with electron capture. The steady — state plasma concentrations of midazolam ranged from 49–385 ng/mL. The total clearance, apparent volume of distribution, and elimination half — life ranged from 0.1–3.1 L/kg/hr, 0.2–3.5 L/kg, and 0.3–10.9 hours, respectively. The marked interpatient variability in pharmacokinetics explains in part, the substantial variation in dosage requirements of midazolam to produce sedation in critically ill pediatric patients.

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References

  1. Blumer JL. Clinical pharmacology of midazolam in infants and children. Clin Pharmacokinet 35: 37–47, 1998.

    CAS  Article  PubMed  Google Scholar 

  2. Nahata MC. Pharmacokinetics of doxacurium during normothermic and hypothermic cardiopulmonary bypass surgery. Can J Anaesth 45: 515–20, 1998.

    Article  Google Scholar 

  3. Allonen H., Ziegler G., Klotz, U.. Midazolam kinetics. Clin Pharmacol Ther 30, 653–61, 1981.

    CAS  Article  PubMed  Google Scholar 

  4. Vasiliades J., Sahawneh T., Midazolam determination by gas chromatography, liquid chromatography and gas chromatography — mass spectrometry. J Chromatogr 228: 195–203, 1982.

    CAS  Article  PubMed  Google Scholar 

  5. Lee TC, Charles BG, Harte GJ, Gray PH, Steer PA, Glenady VJ. Population pharmacokinetic modeling in very premature infants receiving midazolam during mechanical ventilation: midazolam neonatal pharmacokinetics. Anesthesiology 90: 451–7, 1999.

    CAS  Article  PubMed  Google Scholar 

  6. Payne K., Nattheyse FJ, Liebenberg D., Dawes T., The pharmacokinetics of midazolam in paediatric patients. Eur J Clin Pharmacol 37: 267–72, 1989.

    CAS  Article  PubMed  Google Scholar 

  7. Jacqz-Aigrain E., Wood C, and Robieux I. Pharmacokinetics of midazolam in critially ill neonates. Eur J Clin Pharmacol 39: 191–2, 1990.

    CAS  Article  PubMed  Google Scholar 

  8. Jacqz-Aigrain E., Daoud P., Butrin P. Maherzi S., Beaufils F., Pharmacokinetics of midazolam during continuous infusion in critically ill neonates. Eur J Clin Pharmacol 42: 329–32, 1992.

    CAS  Article  PubMed  Google Scholar 

  9. Hartwig, S., Roth B., Theisohn M., Clinical experience with continuous intravenous sedation using midazolam and fentanyl in the paediatric intensive care unit. Eur J Pediatr 150: 784–8, 1991.

    CAS  Article  PubMed  Google Scholar 

  10. Tolia V., Brennan S., Aravind, MK, Kauffman, RE. Pharmacokinetic and pharmacodynamic study of midazolam in children during esophagogastro — duodenoscopy. J. Pediatr 119: 467–71, 1991.

    CAS  Article  PubMed  Google Scholar 

  11. Burtin T., Jacqz-Aigrain E., Girard P., Lenclen R., Magny JF., Betremieux P., Tehiry C., Desplanques L., Mussat P., Population pharmacokinetics of midozolam in neunates. Clin Pharmacol Ther 56: 615–25, 1994.

    CAS  Article  PubMed  Google Scholar 

  12. Kraus GB, Gruber RG, Knoll R., Danner U., Pharmacokinetic studies following intravenous and rectal administration of midazolam in children. Anaesthesist 38: 685–63, 1989.

    Google Scholar 

  13. Bach V., Carl P., Ravlo O., Crawford ME., Jensen AG., Mikkelsen BO., Crevoisier C., Heizmann P., Fattinger K., A randomized comparison between midazolam and thiopental for elective cesarean section: anesthesia: III. Placental transfer and elimination in neonates. Anesth Analg 68: 238–42, 1989.

    CAS  Article  PubMed  Google Scholar 

  14. Mathews HM., Carson IW, Lyons SM., Orr IA., C-upollier PS, Howard PF, Dundee JW. A Pharmacokinetic study of midazolam in paediatric patients Br j Anaesth 61: 302–7, 1988.

    CAS  Article  PubMed  Google Scholar 

  15. Jacqz — Aigrain E., Daoud P., Butrin P., Maherzi S., Beaufil F. Pharmacokinetics of midazolam during continuous infusion in critically ill neonates. Eur J Clin Pharmacol 42: 329–32, 1992.

    Google Scholar 

  16. Rey E., Delaunay L., Pons G., Murat I., Richard MO, Saint — Maurice C., Olive G. Pharmacokinetics of midazolam in children: comparative study of intranasal and intravenous administration. Eur J Clin Pharmacol 41: 355–7, 1991.

    CAS  Article  PubMed  Google Scholar 

  17. Hartwig S., Roth B., Theisohn M. Clinical experience with continuous intravenous sedation using midazolam and fentanyl in the paediatric intensive care unit. Eur J Pediatr 150: 784–8, 1991.

    CAS  Article  PubMed  Google Scholar 

  18. Tolia V., Brennan S., Aravid MK., Kauffman RE. Pharmacokinetic and pharmacodynamic study of midazolam in children during esophagogastro — duodenoscopy. J Pediatr 119:467–71, 1991.

    CAS  Article  PubMed  Google Scholar 

  19. Jacqz — Aigrain E., Wood C., Robieux I. Pharmacokinetics of midazolam in critically ill neonates. Eur J Clin Pharmacol 39: 191–2, 1990.

    Article  Google Scholar 

  20. Jones RD., Chan K., Roulson CJ., Brown AG., Smith ID., Mya GH. Pharmacokinetics of flumazenil and midazolam. Br J Anaesth 70:286–92, 1993.

    CAS  Article  PubMed  Google Scholar 

  21. Tolia V., Brennan S., Aravind MK., Kauffman RE. Pharmacokinetic and pharmacodynamic study of midazolam in children during esophagogastroduodenoscopy. J Pediatr 119: 467–71, 1991.

    CAS  Article  PubMed  Google Scholar 

  22. Hughes J., Gill A., Mulhearn H., Powell E., Choonara I., Stedy state plasma concentration of midazolam in criticaly ill infants and children. Ann Pharmacother 30: 27–30, 1996.

    CAS  PubMed  Google Scholar 

  23. Boulieu R., Lehmann B., Salord F., Fissher C., Morlet D. Pharmacokinetics of midazolam and its main metaboity 1 — hydroxymidazolam in intensive care patients. Eur J Drug Metab Pharmacokinet 23: 255–8, 1998.

    CAS  Article  PubMed  Google Scholar 

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Affiliations

  1. Colleges of Pharmacy and Medicine, The Ohio State University, 500 W. 12th Avenue, 43210, Columbus, OH, U.S.A.

    Milap C. Nahara, Julie McMorrow, Paul R. Jones, David Anglin & Robert Rosenberg

  2. Children’s Research Institute, Children’s Hospital Columbus, 500 W. 12th Avenue, 43210, Columbus, OH, U.S.A.

    Milap C. Nahara, Julie McMorrow, Paul R. Jones, David Anglin & Robert Rosenberg

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  1. Milap C. Nahara
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  2. Julie McMorrow
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  3. Paul R. Jones
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  4. David Anglin
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  5. Robert Rosenberg
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Nahara, M.C., McMorrow, J., Jones, P.R. et al. Pharmacokinetics of midazolam in critically ill pediatric patients. Eur. J. Drug Metab. Pharacokinet. 25, 219–221 (2000). https://doi.org/10.1007/BF03192317

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  • DOI: https://doi.org/10.1007/BF03192317

Keywords

  • Midazolam
  • pharmacokinetics
  • infants
  • children
  • sedation