PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 34021354-6 2021 Furthermore, liver toxicity was only observed in this model when lorlatinib was co-administered with strong CYP3A inducers, and the effects were not restricted to, or exclusively dependent upon, a PXR activation mechanism. lorlatinib 65-75 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 108-113 34021354-2 2021 In a drug-drug-interaction study in healthy human participants, liver enzyme elevations were observed when a single 100 mg dose of lorlatinib was administered after multiple doses of rifampin, a strong cytochrome P450 (CYP) 3 A inducer and a pregnane X receptor (PXR) agonist. lorlatinib 131-141 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 202-227 33937953-2 2021 Lorlatinib is metabolized by cytochrome P450 (CYP) 3A and contraindicated with strong CYP3A inducers because of significant transaminase elevation. lorlatinib 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 29-53 33937953-2 2021 Lorlatinib is metabolized by cytochrome P450 (CYP) 3A and contraindicated with strong CYP3A inducers because of significant transaminase elevation. lorlatinib 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 86-91 33937953-3 2021 This phase I, open-label, two-period study evaluated the impact of a moderate CYP3A inducer, modafinil, on the safety and pharmacokinetics of lorlatinib. lorlatinib 142-152 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 78-83 33937953-10 2021 CONCLUSION: Lorlatinib 100 mg may be safely co-administered with moderate CYP3A inducers. lorlatinib 12-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 74-79 32399810-6 2020 As lorlatinib is both a substrate and inducer of the CYP3A enzyme system and is contraindicated with strong CYP3A inducers, relevant drug-drug interactions are also highlighted. lorlatinib 3-13 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-58 32399810-6 2020 As lorlatinib is both a substrate and inducer of the CYP3A enzyme system and is contraindicated with strong CYP3A inducers, relevant drug-drug interactions are also highlighted. lorlatinib 3-13 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 108-113 31728714-11 2020 Therefore, concomitant use of lorlatinib with strong CYP3A inhibitors should be avoided. lorlatinib 30-40 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-58 31863284-1 2020 INTRODUCTION: Lorlatinib is a third-generation tyrosine kinase inhibitor approved for the treatment of anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer; cytochrome P450 (CYP) 3A plays an important role in the metabolism of lorlatinib. lorlatinib 14-24 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 184-208 31863284-1 2020 INTRODUCTION: Lorlatinib is a third-generation tyrosine kinase inhibitor approved for the treatment of anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer; cytochrome P450 (CYP) 3A plays an important role in the metabolism of lorlatinib. lorlatinib 254-264 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 184-208 31863284-11 2020 These observations support the contraindication in the product label against concomitant use of lorlatinib with all strong CYP3A inducers. lorlatinib 96-106 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 123-128 31728714-2 2020 CYP3A plays a major role in lorlatinib metabolism; therefore, a drug-drug interaction study was warranted to evaluate the impact of the strong CYP3A inhibitor, itraconazole, on lorlatinib plasma exposure. lorlatinib 28-38 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-5 31728714-2 2020 CYP3A plays a major role in lorlatinib metabolism; therefore, a drug-drug interaction study was warranted to evaluate the impact of the strong CYP3A inhibitor, itraconazole, on lorlatinib plasma exposure. lorlatinib 177-187 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-5 29744867-9 2018 In Cyp3a-/- mice, the plasma exposure of lorlatinib was increased 1.3-fold, but was then twofold reduced upon transgenic overexpression of human CYP3A4 in liver and intestine, whereas relative tissue distribution of lorlatinib remained unaltered. lorlatinib 41-51 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 145-151 29744867-11 2018 Moreover, oral availability of lorlatinib is markedly restricted by CYP3A4 activity. lorlatinib 31-41 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 68-74 30660696-4 2019 Upon oral administration of lorlatinib, the plasma AUC0-8h in CYP3A4-humanized mice was ~1.8-fold lower than in wild-type and Cyp3a-/- mice. lorlatinib 28-38 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 62-68 30660696-6 2019 Moreover, simultaneous pharmacological inhibition of P-glycoprotein and CYP3A4 with oral elacridar and ritonavir in CYP3A4-humanized mice profoundly increased lorlatinib brain concentrations, but not its oral availability or other relative tissue distribution. lorlatinib 159-169 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 72-78 30660696-8 2019 The absolute oral bioavailability of lorlatinib over 8 h in wild-type, Cyp3a-/-, and CYP3A4-humanized mice was 81.6%, 72.9%, and 58.5%, respectively. lorlatinib 37-47 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 85-91 30660696-9 2019 Lorlatinib thus has good oral bioavailability, which is markedly restricted by human CYP3A4 but not by mouse Cyp3a. lorlatinib 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 85-91