ArticleCPT: pharmacometrics & systems pharmacology2021
PBPK Model of Coproporphyrin I: Evaluation of the Impact of SLCO1B1 Genotype, Ethnicity, and Sex on its Inter-Individual Variability.
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 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Pyridoxic Acid as Endogenous Biomarker of Renal Organic Anion Transporter Activity: Population Variability and Mechanistic Modeling to Predict Drug-Drug Interactions.CPT: pharmacometrics & systems pharmacology · 2025Pooled it
- Population pharmacokinetic modeling and simulation to support qualification of pyridoxic acid as endogenous biomarker of OAT1/3 renal transporters.CPT: pharmacometrics & systems pharmacology · 2021Trial
- Endogenous Biomarkers to Evaluate Transporter-Mediated Drug-Drug Interactions: Current Evidence, Impact on Clinical Pharmacology Strategy, Remaining Gaps, and Future Directions.Journal of clinical pharmacology · 2026Review
- Impact of Efavirenz on Heme Protein Induction and Biomarkers: Insights From In Vitro Experiments and a Clinical Study.Clinical and translational science · 2026Article
- From Population-Based PBPK to Individualized Virtual Twins: Clinical Validation and Applications in Medicine.Journal of clinical medicine · 2026Review
- Population Pharmacokinetic Modeling of Glycochenodeoxycholic Acid 3-O-Sulfate (GCDCA-S) as Endogenous Biomarker of OATP1B3 and OAT3 Transporters.Clinical pharmacology and therapeutics · 2025Article
- Genotype, Ethnicity, and Drug-Drug Interaction Modeling as Means of Verifying Transporter Biomarker PBPK Model: The Coproporphyrin-I Story.CPT: pharmacometrics & systems pharmacology · 2025Article
- Progress of coproporphyrin as an endogenous biomarker for transporter-mediated drug-drug interactions.Frontiers in pharmacology · 2025Review
- Membrane transporters in drug development and as determinants of precision medicine.Nature reviews. Drug discovery · 2024Review
- Gender Differences in Pharmacokinetics: A Perspective on Contrast Agents.ACS pharmacology & translational science · 2024Review
- Asia-Inclusive Clinical Research and Development Enabled by Translational Science and Quantitative Clinical Pharmacology: Toward a Culture That Challenges the Status Quo.Clinical pharmacology and therapeutics · 2023Article
- The Issue of Pharmacokinetic-Driven Drug-Drug Interactions of Antibiotics: A Narrative Review.Antibiotics (Basel, Switzerland) · 2022Review
- Cluster Gauss-Newton method analyses of PBPK model parameter combinations of coproporphyrin-I based on OATP1B-mediated rifampicin interaction studies.CPT: pharmacometrics & systems pharmacology · 2022Article
- Coproporphyrin I as an Endogenous Biomarker to Detect Reduced OATP1B Activity and Shift in Elimination Route in Chronic Kidney Disease.Clinical pharmacology and therapeutics · 2022Article
- Regulation of Drug Transport Proteins-From Mechanisms to Clinical Impact: A White Paper on Behalf of the International Transporter Consortium.Clinical pharmacology and therapeutics · 2022Review
- Organic Anion Transporting Polypeptide 2B1 (OATP2B1) Genetic Variants:Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Coproporphyrin I (CPI) is an endogenous biomarker of OATP1B activity and associated drug-drug interactions. In this study, a minimal physiologically-based pharmacokinetic model was developed to investigate the impact of OATP1B1 genotype (c.521T>C), ethnicity, and sex on CPI pharmacokinetics and interindividual variability in its baseline. The model implemented mechanistic descriptions of CPI hepatic transport between liver blood and liver tissue and renal excretion. Key model parameters (e.g., endogenous CPI synthesis rate, and CPI hepatic uptake clearance) were estimated by fitting the model simultaneously to three independent CPI clinical datasets (plasma and urine data) obtained from white (n = 16, men and women) and Asian-Indian (n = 26, all men) subjects, with c.521 variants (TT, TC, and CC). The optimized CPI model successfully described the observed data using c.521T>C genotype, ethnicity, and sex as covariates. CPI hepatic active was 79% lower in 521CC relative to the wild type and 42% lower in Asian-Indians relative to white subjects, whereas CPI synthesis was 23% higher in male relative to female subjects. Parameter sensitivity analysis showed marginal impact of the assumption of CPI synthesis site (blood or liver), resulting in comparable recovery of plasma and urine CPI data. Lower magnitude of CPI-drug interaction was simulated in 521CC subjects, suggesting the risk of underestimation of CPI-drug interaction without prior OATP1B1 genotyping. The CPI model incorporates key covariates contributing to interindividual variability in its baseline and highlights the utility of the CPI modeling to facilitate the design of prospective clinical studies to maximize the sensitivity of this biomarker.
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