Population Pharmacokinetics of Oral Gecacitinib in Healthy Subjects and Patients with Autoimmune and Inflammatory Diseases.
Gecacitinib is a novel, broad‐spectrum Janus kinase (JAK) inhibitor being developed for the treatment of myelofibrosis, severe alopecia areata, ankylosing spondylitis, and atopic dermatitis. This study aimed to develop population pharmacokinetic (PopPK) models for gecacitinib and its metabolites ZG0...
| Published in: | Journal of Clinical Pharmacology Vol. 66; no. 6; pp. 1 - 17 |
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| Main Authors: | , , , , , |
| Format: | equations & formulas research tables/charts Journal Article |
| Published: |
Wiley-Blackwell
Jun2026
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=194810484&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 194810484 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00912700 5WH jtl: Journal of Clinical Pharmacology issn: 00912700 maglogo: Y pubinfo: dt: Jun2026 vid: 66 iid: 6 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 194810484 194810484 194810484 10.1002/jcph.70214 194810484 ppf: 1 ppct: 16 formats: tig: atl: Population Pharmacokinetics of Oral Gecacitinib in Healthy Subjects and Patients with Autoimmune and Inflammatory Diseases. aug: au: Meng, Qingheng Zhao, Yuansheng Chen, Wenyang Zhang, Lingxiao Xu, Ling Li, Lujin affil: Center for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China sug: subj: Pharmacokinetics Drug Effects Janus Kinase Inhibitors Pharmacokinetics Autoimmune Diseases Drug Therapy Inflammation Drug Therapy Metabolites Human Male Female Adult Middle Age Aged Dermatitis, Atopic Drug Therapy Alopecia Areata Drug Therapy Spondylitis, Ankylosing Drug Therapy Primary Myelofibrosis Drug Therapy Oxidoreductases Metabolism Drug Interactions Dose-Response Relationship, Drug Administration, Oral Regression Computer Simulation Drug Therapy, Combination Descriptive Statistics Comparative Studies Quality of Life Data Analysis Software Liquid Chromatography-Mass Spectrometry Adult: 19-44 years Middle Aged: 45-64 years Aged: 65+ years Male Female ab: Gecacitinib is a novel, broad‐spectrum Janus kinase (JAK) inhibitor being developed for the treatment of myelofibrosis, severe alopecia areata, ankylosing spondylitis, and atopic dermatitis. This study aimed to develop population pharmacokinetic (PopPK) models for gecacitinib and its metabolites ZG0244 and ZG0245 to evaluate influential factors. Data from healthy subjects and patients across nine clinical trials were pooled. PopPK models were developed using NONMEM, and covariates of interest were tested. The PopPK structure for gecacitinib was a two‐compartment model with first‐order absorption and linear elimination. The metabolite ZG0244 was best described by a two‐compartment model with Michaelis–Menten formation and linear elimination, while for metabolite ZG0245, it was a one‐compartment model with Michaelis–Menten formation and linear elimination. Statistically significant factors affecting pharmacokinetic parameters included sex, age, indication, and co‐administration with a strong CYP3A inducer or inhibitor. The effects of sex, age, and strong CYP3A inducer on exposure were limited, requiring no dose adjustment. A strong CYP3A inhibitor increased exposure by approximately 1.3‐fold. The median time to reach 95% of steady‐state concentration was approximately 3 days for gecacitinib and ZG0244, and approximately 7 days for ZG0245. This study developed population pharmacokinetic models for gecacitinib and its metabolites, and quantified the effects of covariates. pubtype: Academic Journal doctype: equations & formulas research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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