{"doi":"10.1007/s00280-020-04134-9","title":"Population pharmacokinetic analysis of nanoparticle-bound and free camptothecin after administration of NLG207 in adults with advanced solid tumors","abstract":"PURPOSE: NLG207 (formerly CRLX101) is a nanoparticle-drug conjugate (NDC) of the potent topoisomerase I inhibitor, camptothecin (CPT). The present study sought to characterize the complex pharmacokinetics (PK) of NLG207 and better describe CPT release from nanoparticles using a population PK (popPK) model. METHODS: From 27 patients enrolled on two phase II clinical trials (NCT02769962 and NCT03531827), dense sampling was performed up to 48 h post-administration of NLG207 during cycle one and six of treatment; samples were also collected at ~ 360 h post-dose. Conjugated and free CPT concentrations were quantified from each sample, resulting in 477 observations to build a popPK model using non-linear mixed-effects modeling. RESULTS: The PK of NLG207 was characterized by combining two linear two-compartment models with first-order kinetics each to describe nanoparticle-bound (conjugated) and free CPT. Allometric scaling based on body weight provided the best body-size descriptor for all PK parameters. The typical volumes of distribution of the conjugated CPT central and free CPT central compartments were 3.16 L (BSV CV%; 18.1%) and 21.1 L (CV%; 79.8%), respectively. CPT release from the nanoparticle formulation was characterized via an initial rapid clearance of 5.71 L/h (CV%; 62.6%), which decreased via first-order decay (estimated half-life of 0.307 h) to the steady-state value of 0.0988 L/h (CV%; 33.5%) by ~ 4 h after end of infusion. Renal clearance of free CPT was 0.874 L/h (CV%; 42.2%). CONCLUSION: The popPK model confirmed nanoparticle behavior of conjugated CPT and mechanistically characterized CPT release from NLG207. The current analysis provides a strong foundation for future study as a potential predictive tool in ongoing NLG207 clinical trials.","journal":"Cancer Chemotherapy and Pharmacology","year":2020,"id":69957,"datarank":0.7297377984720768,"base_score":3.044522437723423,"endowment":3.044522437723423,"self_citation_contribution":0.4566783656585135,"citation_network_contribution":0.2730594328135632,"self_endowment_contribution":0.4566783656585135,"citer_contribution":0.2730594328135632,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":17,"citers_with_citation_signal":13,"citers_with_endowment":13,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9281,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02769962","NCT03531827"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":370006,"name":"Alwin D. R. Huitema","orcid":"0000-0003-1939-4639","position":1,"is_corresponding":false},{"id":370007,"name":"Thomas P. C. Dorlo","orcid":"0000-0003-3076-8435","position":2,"is_corresponding":false},{"id":109199,"name":"Cody J. Peer","orcid":"0000-0001-9395-3473","position":3,"is_corresponding":false},{"id":256067,"name":"Lisa M. Cordes","orcid":"0000-0003-3833-4084","position":4,"is_corresponding":false},{"id":370008,"name":"Linda Sciuto","orcid":"0000-0001-6314-8991","position":5,"is_corresponding":false},{"id":370652,"name":"Susan Wróblewski","orcid":null,"position":6,"is_corresponding":false},{"id":232027,"name":"Yves Pommier","orcid":"0000-0002-3108-0758","position":7,"is_corresponding":false},{"id":256072,"name":"Ravi A. Madan","orcid":"0000-0001-5106-8636","position":8,"is_corresponding":false},{"id":253875,"name":"Anish Thomas","orcid":"0000-0003-3293-3115","position":9,"is_corresponding":false},{"id":109200,"name":"William D. Figg","orcid":"0000-0003-2428-5613","position":10,"is_corresponding":false},{"id":370005,"name":"Keith T. Schmidt","orcid":"0009-0008-0285-0216","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-18T21:42:48.813846Z","pmid":"32897402","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}