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The linked PBPK models were then used to predict the effect on darunavir or lopinavir exposure from CYP modulators. In the next step, the predicted effect of hepatic impairment was evaluated. Additional exploratory analyses predicted CYP3A inhibition effects on darunavir or lopinavir exposure in simulated hepatically impaired subjects. The linked PBPK models reasonably predicted darunavir or lopinavir exposure based on simulations with CYP inhibitors or inducers. Exploratory simulations using the linked darunavir or lopinavir PBPK models indicated CYP3A inhibition may further increase darunavir or lopinavir exposure in patients with hepatic impairment.</jats:p>","journal":"The Journal of Clinical Pharmacology","year":2017,"id":681131,"datarank":0.4335557636844247,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.0,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":63825,"name":"Ping Zhao","orcid":"0000-0002-5618-0472","position":1,"is_corresponding":false},{"id":1779602,"name":"Vikram Arya","orcid":null,"position":2,"is_corresponding":false},{"id":1779603,"name":"Charu Mullick","orcid":null,"position":3,"is_corresponding":false},{"id":354232,"name":"Kimberly Struble","orcid":"0000-0001-9618-0875","position":4,"is_corresponding":false},{"id":1779605,"name":"Stanley Au","orcid":null,"position":5,"is_corresponding":false},{"id":940887,"name":"Christian Wagner","orcid":"0000-0001-7788-4594","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Physiologically Based Pharmacokinetic Modeling for Predicting the Effect of Intrinsic and Extrinsic Factors on Darunavir or Lopinavir Exposure Coadministered With Ritonavir","abstract":"<jats:title>Abstract</jats:title><jats:p>Management of comorbidities and medications is complex in HIV‐1‐infected patients. 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The linked PBPK models reasonably predicted darunavir or lopinavir exposure based on simulations with CYP inhibitors or inducers. 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