ArticleCPT: pharmacometrics & systems pharmacology2021
Population pharmacokinetic model with time-varying clearance for lorlatinib using pooled data from patients with non-small cell lung cancer and healthy participants.
Article in CPT: pharmacometrics & systems pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Population Pharmacokinetic Modeling Practice of Time-Varying Clearance: Insights from a First-in-Human Study Case.Journal of clinical pharmacology · 2026Trial
- Population pharmacokinetics of mobocertinib in healthy volunteers and patients with non-small cell lung cancer.CPT: pharmacometrics & systems pharmacology · 2022Trial
- Time-Dependent Bias and Prognostic Confounding in Exposure-Response Analysis of Targeted Therapies: Lessons from Sunitinib in Metastatic Renal Cancer.Clinical pharmacology and therapeutics · 2026Article
- A Novel Empirical Autoinduction Model to Characterize the Population Pharmacokinetics and Recommend Dose for Repotrectinib in Adult and Adolescents With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements.CPT: pharmacometrics & systems pharmacology · 2025Article
- Inter-Ethnic Differences in the Efficacy and Safety of Tyrosine Kinase Inhibitors Used in Oncology: Insights From Phase 3 Clinical Trials.Clinical and translational science · 2025Review
- An integrated quantitative systems pharmacology virtual population approach for calibration with oncology efficacy endpoints.CPT: pharmacometrics & systems pharmacology · 2025Article
- Lorlatinib experience in a patient with ALK + non-small cell lung cancer on hemodialysis: A case report.Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners · 2025Article
- Proactive monitoring of drug-drug interactions between direct oral anticoagulants and small-molecule inhibitors in patients with non-small cell lung cancer.British journal of cancer · 2024Observational
- Silibinin Suppresses the Hyperlipidemic Effects of the ALK-Tyrosine Kinase Inhibitor Lorlatinib in Hepatic Cells.International journal of molecular sciences · 2022Article
- Evaluation of Lorlatinib Cerebrospinal Fluid Concentrations in Relation to Target Concentrations for Anaplastic Lymphoma Kinase (ALK) Inhibition.Journal of clinical pharmacology · 2022Article
- Predictiveness of the Human-CYP3A4-Transgenic Mouse Model (Cyp3aXAV) for Human Drug Exposure of CYP3A4-Metabolized Drugs.Pharmaceuticals (Basel, Switzerland) · 2022Article
- A Phase I Study to Evaluate the Pharmacokinetics and Safety of Lorlatinib in Adults with Mild, Moderate, and Severe Renal Impairment.European journal of drug metabolism and pharmacokinetics · 2022Article
- Proton Pump Inhibitors and Cancer: Current State of Play.Frontiers in pharmacology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lorlatinib, a selective inhibitor of anaplastic lymphoma kinase (ALK) and c-ROS oncogene 1 (ROS1) tyrosine kinase, is indicated for the treatment of ALK-positive metastatic non-small cell lung cancer (NSCLC) following progression on crizotinib and at least one other ALK inhibitor, or alectinib/ceritinib as the first ALK inhibitor therapy for metastatic disease. The population pharmacokinetics (PopPK) of lorlatinib was conducted by nonlinear mixed effects modeling of data from 330 patients with ALK-positive or ROS1-positive NSCLC and 95 healthy participants from six phase I studies in healthy volunteers; demographic, metabolizer phenotype, and patient prognostic factors were evaluated as covariates. Lorlatinib plasma PK was well-characterized by a two-compartment model with sequential zero-order and first-order absorption and a time-varying induction of clearance. Single dose clearance was estimated to be 9.04 L/h. Assuming that the metabolic auto-induction of lorlatinib reaches saturation in ~ 5 half-lives, clearance was estimated to approach a maximum of 14.5 L/h at steady-state after a period of ~ 7.25 days. The volume of distribution of the central compartment was estimated to be 121 L and the first-order absorption rate constant was estimated to be 3.1 h
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.