Time course of CYP3A activity during and after metamizole (dipyrone) in healthy volunteers.
cytochrome P-450 CYP3A
dipyrone
drug interaction
enzyme induction
healthy volunteers
midazolam
time factors
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
revised:
02
03
2023
received:
28
12
2022
accepted:
09
03
2023
medline:
21
7
2023
pubmed:
23
3
2023
entrez:
22
3
2023
Statut:
ppublish
Résumé
In patients of all ages, metamizole is a frequently used analgesic. Recently, metamizole has been identified as an inducer of, among others, cytochrome P450 (CYP) 3A activity, but the time course of this interaction has not been evaluated. Using repeated oral microdoses (30 μg) of the CYP3A index substrate midazolam, we assessed changes in midazolam pharmacokinetics (area under the concentration-time curve from 2-4 h: AUC Significant changes in pharmacokinetic parameters were detected already 3 days after start of metamizole treatment. At the steady-state of enzyme induction, the geometric mean ratio of midazolam AUC Metamizole acts as a strong inducer of CYP3A already few days after start of metamizole administration and, thus, should be avoided in patients using drugs with narrow therapeutic index and major clearance via CYP3A. If their administration is essential, close monitoring and dose adjustment of comedication should be performed as early as the first week after the initiation and after discontinuation of metamizole therapy.
Substances chimiques
Midazolam
R60L0SM5BC
Dipyrone
6429L0L52Y
Cytochrome P-450 CYP3A
EC 1.14.14.1
Banques de données
EudraCT
['2020-003984-24']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2458-2464Informations de copyright
© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
Références
Harirforoosh S, Asghar W, Jamali F. Adverse effects of nonsteroidal antiinflammatory drugs: an update of gastrointestinal, cardiovascular and renal complications. J Pharm Pharm Sci. 2013;16(5):821-847. doi:10.18433/J3VW2F
Konijnenbelt-Peters J, van der Heijden C, Ekhart C, Bos J, Bruhn J, Kramers C. Metamizole (dipyrone) as an alternative agent in postoperative analgesia in patients with contraindications for nonsteroidal anti-inflammatory drugs. Pain Pract. 2017;17(3):402-408. doi:10.1111/papr.12467
Klose S, Pflock R, König IR, Linder R, Schwaninger M. Metamizole and the risk of drug-induced agranulocytosis and neutropenia in statutory health insurance data. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(4):681-690. doi:10.1007/s00210-019-01774-4
Guengerich FP. Cytochrome P-450 3A4: regulation and role in drug metabolism. Annu Rev Pharmacol Toxicol. 1999;39(1):1-17. doi:10.1146/annurev.pharmtox.39.1.1
Bachmann F, Duthaler U, Meyer Zu Schwabedissen HE, et al. Metamizole is a moderate cytochrome P450 inducer via the constitutive androstane receptor and a weak inhibitor of CYP1A2. Clin Pharmacol Ther. 2020;109(6):1505-1516. doi:10.1002/cpt.2141
Indiana University DoM-CP. Drug interactions flockhart table: Indiana University - Department of Medicinie; 2021. [updated 2021; cited 2022]. Available from: https://drug-interactions.medicine.iu.edu/MainTable.aspx
Zhou SF. Drugs behave as substrates, inhibitors and inducers of human cytochrome P450 3A4. Curr Drug Metab. 2008;9(4):310-322. doi:10.2174/138920008784220664
Hoffmann F, Meinecke P, Freitag MH, Glaeske G, Schulze J, Schmiemann G. Who gets dipyrone (metamizole) in Germany? Prescribing by age, sex and region. J Clin Pharm Ther. 2015;40(3):285-288. doi:10.1111/jcpt.12261
Lutz M. Metamizole (dipyrone) and the liver: a review of the literature. J Clin Pharmacol. 2019;59(11):1433-1442. doi:10.1002/jcph.1512
Ratiopharm. Fachinformation - Novaminsulfon-ratiopharm®-Tabletten; 2021.
Caraco Y, Zylber-Katz E, Fridlander M, Admon D, Levy M. The effect of short-term dipyrone administration on cyclosporin pharmacokinetics. Eur J Clin Pharmacol. 1999;55(6):475-478. doi:10.1007/s002280050659
Lutz JD, Kirby BJ, Wang L, et al. Cytochrome P450 3A induction predicts P-glycoprotein induction; part 1: establishing induction relationships using ascending dose rifampin. Clin Pharmacol Ther. 2018;104(6):1182-1190. doi:10.1002/cpt.1073
Nassar YM, Hohmann N, Michelet R, et al. Quantification of the time course of CYP3A inhibition, activation, and induction using a population pharmacokinetic model of microdosed midazolam continuous infusion. Clin Pharmacokinet. 2022;61(11):1595-1607. doi:10.1007/s40262-022-01175-6
Breithaupt MH, Krohmer E, Taylor L, et al. Oral bioavailability of microdoses and therapeutic doses of midazolam as a 2-dimensionally printed orodispersible film in healthy volunteers. Eur J Clin Pharmacol. 2022;78(12):1965-1972. doi:10.1007/s00228-022-03406-y
Food and Drug Administration. Drug development and drug interactions: table of substrates, inhibitors and inducers. Food and Drug Administration; 2020. [updated 03.10.2020; cited 2020 11.09.]. Available from: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers#table 2-1
Katzenmaier S, Markert C, Mikus G. Proposal of a new limited sampling strategy to predict CYP3A activity using a partial AUC of midazolam. Eur J Clin Pharmacol. 2010;66(11):1137-1141. doi:10.1007/s00228-010-0878-2
Katzenmaier S, Markert C, Riedel KD, Burhenne J, Haefeli WE, Mikus G. Determining the time course of CYP3A inhibition by potent reversible and irreversible CYP3A inhibitors using a limited sampling strategy. Clin Pharmacol Ther. 2011;90(5):666-673. doi:10.1038/clpt.2011.164
Burhenne J, Halama B, Maurer M, et al. 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(7):2439-2450. doi:10.1007/s00216-011-5675-y
Alexander SP, Kelly E, Mathie A, et al. The concise guide to pharmacology 2021/22: transporters. Br J Pharmacol. 2021;178(Suppl 1):S412-s513. doi:10.1111/bph.15540
Alexander SP, Fabbro D, Kelly E, et al. The concise guide to pharmacology 2021/22: enzymes. Br J Pharmacol. 2021;178(Suppl 1):S313-s411. doi:10.1111/bph.15540
Ludwig WD, Mühlbauer B, Seifert R. Arzneiverordnungs-Report 2021. Vol. XVII. Springer Berlin; 2021. 837 p.
European Medicines Agency. Guideline on the investigation of drug interactions. European Union; 2012. [updated 01.01.2013; cited 2022]. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-investigation-drug-interactions-revision-1_en.pdf
Imai H, Kotegawa T, Tsutsumi K, et al. The recovery time-course of CYP3A after induction by St John's wort administration. Br J Clin Pharmacol. 2008;65(5):701-707. doi:10.1111/j.1365-2125.2008.03120.x
Kapetas AJ, Sorich MJ, Rodrigues AD, Rowland A. Guidance for rifampin and midazolam dosing protocols to study intestinal and hepatic cytochrome P450 (CYP) 3A4 induction and de-induction. AAPS J. 2019;21(5):78. doi:10.1208/s12248-019-0341-y
Inui N, Akamatsu T, Uchida S, et al. Chronological effects of rifampicin discontinuation on cytochrome P450 activity in healthy Japanese volunteers, using the cocktail method. Clin Pharmacol Ther. 2013;94(6):702-708. doi:10.1038/clpt.2013.167
Yang J, Liao M, Shou M, et al. Cytochrome p450 turnover: regulation of synthesis and degradation, methods for determining rates, and implications for the prediction of drug interactions. Curr Drug Metab. 2008;9(5):384-394. doi:10.2174/138920008784746382
Hernandez JP, Mota LC, Huang W, Moore DD, Baldwin WS. Sexually dimorphic regulation and induction of P450s by the constitutive androstane receptor (CAR). Toxicology. 2009;256(1-2):53-64. doi:10.1016/j.tox.2008.11.002
Wolbold R, Klein K, Burk O, et al. Sex is a major determinant of CYP3A4 expression in human liver. Hepatology. 2003;38(4):978-988. doi:10.1002/hep.1840380424
Levy M, Zylber-Katz E, Rosenkranz B. Clinical pharmacokinetics of dipyrone and its metabolites. Clin Pharmacokinet. 1995;28(3):216-234. doi:10.2165/00003088-199528030-00004
Saussele T, Burk O, Blievernicht JK, et al. Selective induction of human hepatic cytochromes P450 2B6 and 3A4 by metamizole. Clin Pharmacol Ther. 2007;82(3):265-274. doi:10.1038/sj.clpt.6100138
Tian D, Hu Z. CYP3A4-mediated pharmacokinetic interactions in cancer therapy. Curr Drug Metab. 2014;15(8):808-817. doi:10.2174/1389200216666150223152627
de Jonge ME, Huitema AD, van Dam SM, Beijnen JH, Rodenhuis S. Significant induction of cyclophosphamide and thiotepa metabolism by phenytoin. Cancer Chemother Pharmacol. 2005;55(5):507-510. doi:10.1007/s00280-004-0922-y
Stage TB, Graff M, Wong S, et al. Dicloxacillin induces CYP2C19, CYP2C9 and CYP3A4 in vivo and in vitro. Br J Clin Pharmacol. 2018;84(3):510-519. doi:10.1111/bcp.13467
Cynke E, Binet I, Haefeli W, Thiel G (Eds). Flucloxacillin & cyclosporine a: an unrecognised but relevant interaction in renal transplant recipients. Kidney international. BLACKWELL SCIENCE INC; 1999.
van Erp NP, Guchelaar HJ, Ploeger BA, Romijn JA, Hartigh J, Gelderblom H. Mitotane has a strong and a durable inducing effect on CYP3A4 activity. Eur J Endocrinol. 2011;164(4):621-626. doi:10.1530/EJE-10-0956
Ruschitzka F, Meier PJ, Turina M, Lüscher TF, Noll G. Acute heart transplant rejection due to Saint John's wort. Lancet. 2000;355(9203):548-549. doi:10.1016/S0140-6736(99)05467-7
Saari TI, Laine K, Leino K, Valtonen M, Neuvonen PJ, Olkkola KT. Effect of voriconazole on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam. Clin Pharmacol Ther. 2006;79(4):362-370. doi:10.1016/j.clpt.2005.12.305