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Clinical Drug Investigation

, Volume 9, Issue 3, pp 131–140 | Cite as

Early Pharmacokinetics of Midazolam

Sampling Site and Schedule Considerations
  • V. Mastey
  • F. Donati
  • F. Varin
Original Research Clinical Pharmacokinetics

Summary

The influence of sampling site and sampling schedule on the early pharmacokinetics of a lipophilic drug, midazolam, was studied in 6 anaesthetised patients following an intravenous bolus injection of 0.05 mg/kg. Arterial and venous blood samples were drawn simultaneously over a period of 180 minutes. An extensive sampling procedure was used during the initial distribution phase; specifically, 12 arterial and 4 venous samples within the first 2 minutes. Midazolam concentrations were measured by high-performance liquid chromatography. Compared with peak venous concentrations, peak arterial concentrations were 2-fold greater and were reached 1 minute earlier. Although arterial concentrations exceeded corresponding venous concentrations for up to 90 minutes, a significant arteriovenous difference was observed during the first 2 minutes only. Consequently, noncompartmental pharmacokinetic parameters (mean residence time, volume of distribution at steady-state, total body clearance) obtained from arterial and venous values did not differ significantly. In addition, similar results were obtained for pharmacokinetic parameters using either the complete (continuous sampling over 2 minutes) or limited (assuming 1- and 2-minute samples only) arterial data set. It is concluded that both the sampling site and the sampling schedule altered the initial plasma concentration-time profile of midazolam. Although neither of these factors had a strong influence on the overall pharmacokinetic parameters of midazolam, their potential effect on the pharmacokinetic/pharmacodynamic relationship of midazolam during the onset phase should be considered.

Keywords

Midazolam Drug Invest Atracurium Mean Residence Time Mivacurium 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Adis International Limited 1995

Authors and Affiliations

  • V. Mastey
    • 1
  • F. Donati
    • 2
  • F. Varin
    • 1
  1. 1.Faculté de PharmacieUniversité de MontréalMontréalCanada
  2. 2.Department of AnaesthesiaMcGill UniversityMontrealCanada

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