Können Lebensmittel die Metabolisierung von Idelalisib beeinflussen?

Zusammenfassung

Seit Mitte des Jahres 2014 steht mit Idelalisib (Zydelig) ein neuer Arzneistoff in der Behandlung von leukämischen Erkrankungen zur Verfügung. Idelalisib wird hauptsächlich von der Aldehydoxidase (ca. 70 %) und zu einem geringeren Teil von der Isoform CYP3A4 (ca. 30 %) zu dem Hauptmetaboliten GS-563117 verstoffwechselt. Uridin-5’-diphospho-glucuronosyltransferase 1A4 (UGT1A4) ist zu einem unwesentlichen Teil an der Metabolisierung beteiligt.

Obwohl gemäß der Arzneimittel-Begleitinformation eine Applikation ohne Berücksichtigung der Ernährung erfolgen kann, sollte man beachten, dass einige pflanzliche Sekundärmetabolite aus der täglichen Nahrung durchaus die Metabolisierung von Idelalisib, auch bei zeitversetzter Applikation, beeinflussen könnten.

Summary

Since mid of 2014 Idelalisib is available as a new drug for the treatment of leukemic diseases. Idelalisib is mainly metabolized by aldehyde oxidase (ca. 70 %) and to a minor extend by the isoform CYP 3A4 (ca. 30 %) to the main metabolite GS-563117. Uridin-5’-diphospho-glucuronosyltransferase 1A4 (UGT 1A4) plays a marginal role in metabolising.

According to the accompanying drug information an application can take place without consideration of the diet. Although you should note that some herbal secondary metabolites from the daily diet could definitely affect the metabolism of Idelalisib, even with time-delayed application.

Schlüsselwörter

Idelalisib - Ernährung - Sekundärmetabolite - Metabolisierung

Keywords

Idelalisib - nutrition - secondary metabolites - metabolism

• Literatur

• 1 Barr JT, Jones JP, Oberlies NH, Paine MF. Inhibition of human aldehyde oxidase activity by diet-derived constituents: structural influence, enzyme-ligand interactions, and clinical relevance. Drug Metab Dispos 2015; 43(1): 34-41
• 2 DFG – Senatskommission zur Beurteilung der gesundheitlichen Unbedenklichkeit von Lebensmitteln: Toxikologische Beurteilung von Furocumarinen in Lebensmitteln. Protokoll vom September 2004, aktualisiert in der Fassung vom 25. Januar 2010
• 3 EMA Press release 25/07/2014. European Medicines Agency recommends approval of two new treatment options for rare cancers: Imbruvica and Zydelig to be used in different forms of blood cancers.
• 4 Gilead Sciences Canada, Inc. Mississauga. ON L5N 2W3, Product Monograph Pr ZYDELIG™ Idelalisib Tablets 150 mg/100 mg, 25 March 2015.
• 5 Gufford BT, Chen G, Lazarus P et al. Identification of diet-derived constituents as potent inhibitors of intestinal glucuronidation. Drug Metab Dispos 2014; 42(10): 1675-1683
• 6 Hamzeh-Mivehroud M, Rahmani S, Rashidi MR et al. Structure-based investigation of rat aldehyde oxidase inhibition by flavonoids. Xenobiotica 2013; 43(8): 661-670
• 7 Hamzeh-Mivehroud M, Rahmani S, Feizi MA et al. In vitro and in silico studies to explore structural features of flavonoids for aldehyde oxidase inhibition. Arch Pharm 2014; 347(10): 738-747
• 8 Jin F, Robeson M, Zhou H et al. Clinical drug interaction profile of idelalisib in healthy subjects. J Clin Pharmacol 2015; Mar 11. DOI: 10.1002/jcph.495.
• 9 Jin F, Robeson M, Zhou H et al. The pharmacokinetics and safety of idelalisib in subjects with moderate or severe hepatic impairment. J Clin Pharmacol 2015; Mar 27. DOI: 10.1002/jcph.504.
• 10 Keating GM. Idelalisib: a review of its use in chronic lymphocytic leukaemia and indolent non-Hodgkin’s lymphoma. Target Oncol 2015; 10(1): 141-151
• 11 Kronabel D. Possible influence of some foods on the metabolism of ibrutinib. Clin Lab 2015; 61: 443-444
• 12 Miller BW, Przepiorka D, de Claro RA et al. FDA approval: idelalisib monotherapy for the treatment of patients with follicular lymphoma and small lymphocytic lymphoma. Clin Cancer Res 2015; 21(7): 1525-1529
• 13 Obach RS, Huynh P, Allen MC, Beedham C. Human liver aldehyde oxidase: inhibition by 239 drugs. J Clin Pharmacol 2004; 44(1): 7-19
• 14 Pirouzpanah S, Hanaee J, Razavieh SV, Rashidi MR. Inhibitory effects of flavonoids on aldehyde oxidase activity. J Enzyme Inhib Med Chem 2009; 24(1): 14-21
• 15 Tayama Y, Sugihara K, Sanoh S et al. Effect of tea beverages on aldehyde oxidase activity. Drug Metab Pharmacokinet 2011; 26(1): 94-101
• 16 Williams JA, Hyland R, Jones BC et al. Drug-Drug Interactions for UDP-Glucuronsyltrasferase Substrates a Pharmacokinetic Explanation for typically observed low Exposure (AUCI/AUC) Ratios. DMD 2004; 32(11): 1201-1208
• 17 Yang J, Yan B. Photochemotherapeutic agent 8-methoxypsoralen induces cytochrome P450 3A4 and carboxylesterase HCE2: evidence on an involvement of the pregnane X receptor. Toxicol Sci 2007; 95(1): 13-22
• 18 Yang Q, Modi P, Newcomb T et al. Idelalisib: First-in-class PI3K delta inhibitor for the treatment of chronic lymphocytic leukemia, small lymphocytic leukemia, and follicular lymphoma. Clin Cancer Res 2015; 21(7): 1537-1542