{"id":"W3208200825","doi":"10.1124/dmd.121.000637","title":"In Defense of Current Concepts and Applications of Clearance in Drug Development and Therapeutics","year":2021,"lang":"en","type":"letter","venue":"Drug Metabolism and Disposition","topic":"Pharmacogenetics and Drug Metabolism","field":"Pharmacology, Toxicology and Pharmaceutics","cited_by":15,"is_retracted":false,"has_abstract":false,"ca_institutions":"University of Toronto","funders":"Medical Research Council; Natural Sciences and Engineering Research Council of Canada","keywords":"Physiologically based pharmacokinetic modelling; Metabolic clearance rate; Pharmacokinetics; Clearance; Drug; Pharmacology; Drug development; Clearance rate; Intensive care medicine; Medicine; Extrapolation; Chemistry; Mathematics; Internal medicine; Urology; Statistics","routes":{"ca_aff":true,"ca_fund":true,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":false},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.01765667,0.002209089,0.004176136,0.001347652,0.008662057,0.01913614,0.00597702,0.177634,0.006149904],"category_scores_gemma":[0.06342467,0.001680619,0.00302778,0.001809781,0.01387596,0.01030744,0.005838569,0.1405323,0.007395194],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.01395136,"about_ca_system_score_gemma":0.01649949,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.01254154,"about_ca_topic_score_gemma":0.02532258,"domain_scores_codex":[0.9786945,0.006233847,0.002407859,0.002837116,0.007694886,0.002131756],"domain_scores_gemma":[0.9620554,0.02399398,0.002889826,0.001151101,0.005905115,0.004004561],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"not_applicable","study_design_gemma":"not_applicable","study_design_scores_codex":[0.0001017529,0.00005940521,0.0005600934,0.0001201068,0.00005013506,0.001518393,0.0003671368,0.0001898094,0.0002670561,0.02476567,0.9584662,0.01353425],"study_design_scores_gemma":[0.0001684987,0.000112488,0.0007417657,0.0004729788,0.00006825347,0.001131378,0.0004207949,0.001312292,0.0002643183,0.04797598,0.9472244,0.000106837],"study_design_candidate":"not_applicable","study_design_consensus":"not_applicable","genre_codex":"commentary","genre_gemma":"commentary","genre_scores_codex":[0.0001393662,0.001952263,0.000366729,0.9755552,0.01945184,0.000013865,0.00002242072,0.00002109176,0.002477338],"genre_scores_gemma":[0.0014805,0.0009276474,0.0005211161,0.9496171,0.04149834,0.00004949963,0.00001054995,0.00001502231,0.005880119],"genre_candidate":"commentary","genre_consensus":"commentary","teacher_disagreement_score":0.177634,"threshold_uncertainty_score":0.1012247,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.05631929325157674,"score_gpt":0.3964351982274604,"score_spread":0.3401159049758836,"validation_status":"score_only:v0-immature-baseline","note":"Baseline scores from an immature model (maturity gate not passed). Scores rank; they never assert a category."}}