European Journal of Clinical Pharmacology

, Volume 60, Issue 4, pp 231–236 | Cite as

Pharmacokinetics of midazolam in CYP3A4- and CYP3A5-genotyped subjects

  • Chin B. Eap
  • Thierry Buclin
  • Elisabeth Hustert
  • Gabriela Bleiber
  • Kerry Powell Golay
  • Anne-Catherine Aubert
  • Pierre Baumann
  • Amalio Telenti
  • Reinhold Kerb



We investigated whether differences in pharmacokinetics of midazolam, a CYP3A probe, could be demonstrated between subjects with different CYP3A4 and CYP3A5 genotypes.


Plasma concentrations of midazolam, and of total (conjugated + unconjugated) 1′OH-midazolam, and 4′OH-midazolam were measured after the oral administration of 7.5 mg or of 75 µg of midazolam in 21 healthy subjects.


CYP3A5*7, CYP3A4*1E, CYP3A4*2, CYP3A4*4, CYP3A4*5, CYP3A4*6, CYP3A4*8, CYP3A4*11, CYP3A4*12, CYP3A4*13, CYP3A4*17 and CYP3A4*18 alleles were not identified in the 21 subjects. CYP3A5*3, CYP3A5*6, CYP3A4*1B and CYP3A4*1F alleles were identified in 20, 1, 4 and 2 subjects, respectively. No statistically significant differences were observed for the AUCinf values between the different genotypes after the 75-µg or the 7.5-mg dose.


Presently, CYP3A4 and CYP3A5 genotyping methods do not sufficiently reflect the inter-individual variability of CYP3A activity.


CYP3A4 CYP3A5 Phenotyping 



The authors thank Mrs V. Sari and Mrs C. Bertschi for editorial assistance, Mrs E. Ponce, Mrs J. Rosselet and Mrs M. Gobin for bibliographic help. This work was supported in part by the Swiss National Research Foundation (project 3200–065427.01).


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Chin B. Eap
    • 1
  • Thierry Buclin
    • 2
  • Elisabeth Hustert
    • 3
  • Gabriela Bleiber
    • 4
  • Kerry Powell Golay
    • 1
  • Anne-Catherine Aubert
    • 1
  • Pierre Baumann
    • 1
  • Amalio Telenti
    • 4
  • Reinhold Kerb
    • 3
  1. 1.Unit of Biochemistry and Clinical Psychopharmacology, Centre of Psychiatric NeurosciencesUniversity Department of Adult Psychiatry, Hôpital de CeryPrilly-LausanneSwitzerland
  2. 2.Department of Clinical PharmacologyUniversity Hospital of LausanneSwitzerland
  3. 3.EPIDAUROS Biotechnologie AGBernriedGermany
  4. 4.Division of Infectious DiseasesUniversity Hospital of LausanneSwitzerland

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