Effect of rifampin and itraconazole on the pharmacokinetics of zanubrutinib (a Bruton's tyrosine kinase inhibitor) in Asian and non-Asian healthy subjects.
Purpose: Zanubrutinib (BGB-3111) is a potent Bruton's tyrosine kinase inhibitor with promising clinical activity in B-cell malignancies. Zanubrutinib was shown to be mainly metabolized through cytochrome P450 3A (CYP3A) in vitro. We evaluated the effect of steady-state rifampin (a strong CYP3A induc...
| Publicado en: | Cancer Chemotherapy & Pharmacology Vol. 85; no. 2; pp. 391 - 400 |
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| Autores principales: | , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Springer Nature
Feb2020
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=141728221&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 141728221 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 03445704 NO9 jtl: Cancer Chemotherapy & Pharmacology issn: 03445704 maglogo: N pubinfo: dt: Feb2020 vid: 85 iid: 2 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 141728221 141728221 NLM31875923 141728221 10.1007/s00280-019-04015-w NLM31875923 141728221 ppf: 391 ppct: 9 formats: tig: atl: Effect of rifampin and itraconazole on the pharmacokinetics of zanubrutinib (a Bruton's tyrosine kinase inhibitor) in Asian and non-Asian healthy subjects. aug: au: Mu, Song Tang, Zhiyu Novotny, William Tawashi, Manal Li, Ta-Kai Ou, Ying Sahasranaman, Srikumar affil: Clinical Pharmacology, BeiGene USA, 2955 Campus Drive, Suite 300, 94403, San Mateo, CA, USA sug: subj: Protein Kinase Inhibitors Pharmacokinetics Oxidoreductases Therapeutic Use Piperidines Pharmacokinetics Rifampin Therapeutic Use Itraconazole Therapeutic Use Heterocyclic Compounds Pharmacokinetics Oxidoreductases Antagonists and Inhibitors Aged Oxidoreductases Metabolism Human Male Research Subjects Middle Age Drug Interactions Young Adult Pharmacokinetics Adolescence Female Adult Validation Studies Comparative Studies Evaluation Research Multicenter Studies Scales Aged: 65+ years Middle Aged: 45-64 years Adolescent: 13-18 years Adult: 19-44 years Male Female ab: Purpose: Zanubrutinib (BGB-3111) is a potent Bruton's tyrosine kinase inhibitor with promising clinical activity in B-cell malignancies. Zanubrutinib was shown to be mainly metabolized through cytochrome P450 3A (CYP3A) in vitro. We evaluated the effect of steady-state rifampin (a strong CYP3A inducer) and steady-state itraconazole (a strong CYP3A inhibitor) on the pharmacokinetics (PK), safety, and tolerability of zanubrutinib in healthy Asian and non-Asian subjects.Methods: In this open-label, two-part clinical study, 20 participants received a single oral dose of zanubrutinib (320 mg) and oral rifampin (600 mg) in Part A, and 18 participants received a single oral dose of zanubrutinib (20 mg) and oral itraconazole (200 mg) in Part B. Serial blood samples were collected after administration of zanubrutinib alone and zanubrutinib in combination with rifampin or itraconazole for the measurement of PK parameters.Results: Coadministration with rifampin decreased AUC0-∞ of zanubrutinib by 13.5-fold and Cmax by 12.6-fold. Coadministration with itraconazole increased the AUC0-∞ of zanubrutinib by 3.8-fold and Cmax by 2.6-fold. The PK of zanubrutinib was consistent between Asian and non-Asian subjects, and zanubrutinib was well tolerated in this study.Conclusions: These results confirm that zanubrutinib is primarily metabolized by CYP3A in humans. The PK of zanubrutinib was comparable between Asian and non-Asian subjects and, therefore, no dose modifications are necessary for zanubrutinib in these ethnic populations. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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