Midazolam microdose to determine systemic and pre-systemic metabolic CYP3A activity in humans

British Journal of Clinical Pharmacology

Volumn 79, Issue 2, 2015, Pages 278-285

  Hohmann, Nicolas ^a   Kocheise, Franziska ^a   Carls, Alexandra ^a   Burhenne, Jürgen ^a   Haefeli, Walter E ^a   Mikus, Gerd ^a  

^a UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

CYP3A; microdosing; midazolam; phenotyping; UPLC MS MS

Indexed keywords

CYTOCHROME P450 3A; MIDAZOLAM;

ADULT; AREA UNDER THE CURVE; ARTICLE; CONTINUOUS INFUSION; CROSSOVER PROCEDURE; DROWSINESS; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DETERMINATION; DRUG DISPOSITION; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG HALF LIFE; DRUG MICRODOSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG URINE LEVEL; ENZYME ACTIVITY; EXTRACTION RATIO; FEMALE; GUT EXTRACTION RATIO; HEPATIC EXTRACTION RATIO; HUMAN; LIMIT OF QUANTITATION; LIQUID CHROMATOGRAPHY; LIVER BLOOD FLOW; MALE; MAXIMUM PLASMA CONCENTRATION; METABOLIC CLEARANCE; NORMAL HUMAN; OPEN STUDY; ORAL CLEARANCE; PRIORITY JOURNAL; SINGLE DRUG DOSE; SOMNOLENCE; TANDEM MASS SPECTROMETRY; TIME TO MAXIMUM PLASMA CONCENTRATION; VOLUME OF DISTRIBUTION; VOLUME OF DISTRIBUTION AT STEADY-STATE; ADOLESCENT; BIOAVAILABILITY; COMPARATIVE STUDY; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOSE RESPONSE; METABOLISM; MIDDLE AGED; YOUNG ADULT;

ADOLESCENT; ADULT; AREA UNDER CURVE; BIOLOGICAL AVAILABILITY; CROSS-OVER STUDIES; CYTOCHROME P-450 CYP3A; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HUMANS; MALE; MIDAZOLAM; MIDDLE AGED; YOUNG ADULT;

EID: 84941181029     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/bcp.12502     Document Type: Article

References (26)

1. Evans WE, Relling MV,. Pharmacogenomics: translating functional genomics into rational therapeutics. Science 1999; 286: 487-491.
2. Paine MF, Hart HL, Ludington SS, Haining RL, Rettie AE, Zeldin DC,. The human intestinal cytochrome P450 'pie'. Drug Metab Dispos 2006; 34: 880-886.
3. Dresser GK, Spence JD, Bailey DG,. Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet 2000; 38: 41-57.
4. CDER. Guidance for industry drug interaction studies-study design, data analysis, implications for dosing, and labeling recommendations. 2012, Available at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm292362.pdf (last accessed 19 August 2014).
5. EMA. Guideline on the investigation of drug interactions. 2012, Available at http://www.ema.europa.eu/docs/en-GB/document-library/Scientific-guideline/2012/07/WC500129606.pdf (last accessed 19 August 2014).
6. Arendt RM, Greenblatt DJ, Garland WA,. Quantitation by gas chromatography of the 1- and 4-hydroxy metabolites of midazolam in human plasma. Pharmacology 1984; 29: 158-164.
7. Seo KA, Bae SK, Choi YK, Choi CS, Liu KH, Shin JG,. Metabolism of 1'- and 4-hydroxymidazolam by glucuronide conjugation is largely mediated by UDP-glucuronosyltransferases 1A4, 2B4, and 2B7. Drug Metab Dispos 2010; 38: 2007-2013.
8. Heizmann P, Eckert M, Ziegler WH,. Pharmacokinetics and bioavailability of midazolam in man. Br J Clin Pharmacol 1983; 16 (Suppl. 1): 43S-49.
9. Thummel KE, Shen DD, Podoll TD, Kunze KL, Trager WF, Hartwell PS, Raisys VA, Marsh CL, McVicar JP, Barr DM,. Use of midazolam as a human cytochrome P450 3A probe: I. In vitro-in vivo correlations in liver transplant patients. J Pharmacol Exp Ther 1994; 271: 549-556.
10. Fuhr U, Jetter A, Kirchheiner J,. Appropriate phenotyping procedures for drug metabolizing enzymes and transporters in humans and their simultaneous use in the 'cocktail' approach. Clin Pharmacol Ther 2007; 81: 270-283.
11. Halama B, Hohmann N, Burhenne J, Weiss J, Mikus G, Haefeli WE,. A nanogram dose of the CYP3A probe substrate midazolam to evaluate drug interactions. Clin Pharmacol Ther 2013; 93: 564-571.
12. Hohmann N, Halama B, Siller N, Mikus G, Haefeli WE,. Response to 'can CYP3A activity be evaluated for drug interaction using a nanogram dose of probe drug?': evaluation of CYP3A activity with microdoses of midazolam. Clin Pharmacol Ther 2014; 95: 490-491.
13. Lappin G, Kuhnz W, Jochemsen R, Kneer J, Chaudhary A, Oosterhuis B, Drijfhout WJ, Rowland M, Garner RC,. Use of microdosing to predict pharmacokinetics at the therapeutic dose: experience with 5 drugs. Clin Pharmacol Ther 2006; 80: 203-215.
14. Burhenne J, Halama B, Maurer M, Riedel KD, Hohmann N, Mikus G, Haefeli WE,. Quantification of femtomolar concentrations of the CYP3A substrate midazolam and its main metabolite 1'-hydroxymidazolam in human plasma using ultra performance liquid chromatography coupled to tandem mass spectrometry. Anal Bioanal Chem 2012; 402: 2439-2450.
15. Hafner V, Jäger M, Matthée AK, Ding R, Burhenne J, Haefeli WE, Mikus G,. Effect of simultaneous induction and inhibition of CYP3A by St John's Wort and ritonavir on CYP3A activity. Clin Pharmacol Ther 2010; 87: 191-196.
16. Lee JI, Chaves-Gnecco D, Amico JA, Kroboth PD, Wilson JW, Frye RF,. Application of semisimultaneous midazolam administration for hepatic and intestinal cytochrome P450 3A phenotyping. Clin Pharmacol Ther 2002; 72: 718-728.
17. Yuan R, Madani S, Wei XX, Reynolds K, Huang SM,. Evaluation of cytochrome P450 probe substrates commonly used by the pharmaceutical industry to study in vitro drug interactions. Drug Metab Dispos 2002; 30: 1311-1319.
18. Hamaoka N, Oda Y, Hase I, Asada A,. Cytochrome P4502B6 and 2C9 do not metabolize midazolam: kinetic analysis and inhibition study with monoclonal antibodies. Br J Anaesth 2001; 86: 540-544.
19. Eap CB, Fellay J, Buclin T, Bleiber G, Golay KP, Brocard M, Baumann P, Telenti A,. CYP3A activity measured by the midazolam test is not related to 3435 C >T polymorphism in the multiple drug resistance transporter gene. Pharmacogenetics 2004; 14: 255-260.
20. Ziesenitz VC, Weiss J, Haefeli WE, Mikus G,. Cytochrome P450-3A phenotyping using midazolam is not altered by OATP1B1 polymorphisms. Clin Pharmacol Ther 2013; 93: 388.
21. Eap CB, Buclin T, Cucchia G, Zullino D, Hustert E, Bleiber G, Golay KP, Aubert AC, Baumann P, Telenti A, Kerb R,. Oral administration of a low dose of midazolam (75 microg) as an in vivo probe for CYP3A activity. Eur J Clin Pharmacol 2004; 60: 237-246.
22. Croft M, Keely B, Morris I, Tann L, Lappin G,. Predicting drug candidate victims of drug-drug interactions, using microdosing. Clin Pharmacokinet 2012; 51: 237-246.
23. Kharasch ED, Jubert C, Senn T, Bowdle TA, Thummel KE,. Intraindividual variability in male hepatic CYP3A4 activity assessed by alfentanil and midazolam clearance. J Clin Pharmacol 1999; 39: 664-669.
24. Nakamura K, Watanabe A, Okudaira N, Okazaki O, Sudo K,. Effect of ion suppression on judgment of enzyme inhibition and avoidance of error by utilizing a stable isotope-labeled probe substrate: example of CYP3A4 inhibition with [13C4,15N] labeled midazolam as a substrate. Drug Metab Pharmacokinet 2007; 22: 113-118.
25. Theile D, Mikus G,. Deceptive argumentation against diagnostic microdosing of anticancer drugs. Int J Cancer 2014; 135: 1753-1754.
26. Mathijssen RH, de Jong FA, van Schaik RH, Lepper ER, Friberg LE, Rietveld T, de Bruijn P, Graveland WJ, Figg WD, Verweij J, Sparreboom A,. Prediction of irinotecan pharmacokinetics by use of cytochrome P450 3A4 phenotyping probes. J Natl Cancer Inst 2004; 96: 1585-1592.