Physiologically based pharmacokinetic modeling of small molecules: How much progress have we made?

N Isoherranen - Drug Metabolism and Disposition, 2024 - Elsevier
Physiologically based pharmacokinetic (PBPK) models of small molecules have become
mainstream in drug development and in academic research. The use of PBPK models is …

Innovations, opportunities, and challenges for predicting alteration in drug-metabolizing enzyme and transporter activity in specific populations

PP Chothe, V Arya, B Prasad, D Ramsden… - Drug Metabolism and …, 2023 - Elsevier
Drug-metabolizing enzymes and transporters (DMETs) are key regulators of the
pharmacokinetics, efficacy, and toxicity of therapeutics. Over the past two decades …

Phase 1 pharmacokinetic and safety study of soticlestat in participants with mild or moderate hepatic impairment or normal hepatic function

W Yin, P Mitra, V Copalu, TC Marbury… - Pharmacology …, 2024 - Wiley Online Library
Abstract This phase 1, open‐label, three‐arm study (NCT05098054) compared the
pharmacokinetics and safety of soticlestat (TAK‐935) in participants with hepatic impairment …

Incorporation and performance verification of hepatic portal blood flow shunting in minimal and full PBPK models of liver cirrhosis

BG Small, O Hatley, M Jamei, I Gardner… - Clinical …, 2023 - Wiley Online Library
Patho‐physiological changes in liver cirrhosis create portacaval shunts that allow blood flow
to bypass the hepatic portal vein into the systemic circulation affecting drug …

Simultaneously predicting the pharmacokinetics of ces1-metabolized drugs and their metabolites using physiologically based pharmacokinetic model in cirrhosis …

X Luo, Z Zhang, R Mu, G Hu, L Liu, X Liu - Pharmaceutics, 2024 - mdpi.com
Hepatic carboxylesterase 1 (CES1) metabolizes numerous prodrugs into active ingredients
or direct-acting drugs into inactive metabolites. We aimed to develop a semi-physiologically …

Toward improved predictions of pharmacokinetics of transported drugs in hepatic impairment: Insights from the extended clearance model

F Storelli, MK Ladumor, X Liang, Y Lai… - CPT …, 2024 - Wiley Online Library
Abstract Hepatic impairment (HI) moderately (< 5‐fold) affects the systemic exposure (ie,
area under the plasma concentration–time curve [AUC]) of drugs that are substrates of the …

[HTML][HTML] Disposition of Oral Nalbuphine and Its Metabolites in Healthy Subjects and Subjects with Hepatic Impairment: Preliminary Modeling Results Using a …

S Nagar, A Hawi, T Sciascia, K Korzekwa - Metabolites, 2024 - mdpi.com
Nalbuphine (NAL) is a mixed κ-agonist/μ-antagonist opioid with extensive first-pass
metabolism. A phase 1 open-label study was conducted to characterize the …