The absolute oral bioavailability (BA) of drugs are yet to be determined, and intravenous pharmacokinetic studies are currently considered indispensable for determining the BA values of oral drugs. The aim of this study was to develop and validate a novel approach to estimating BA values without intravenous pharmacokinetic data. Based on the drug inclusion criteria, such as exhibiting a urinary recovery rate of (R) of ≥20% in a clinical study, 13 drugs were included in the present study, and pharmacokinetic data for them were collected from the literature. The fraction excreted unchanged into urine (f) was calculated for healthy subjects by dividing the R value by the total recovery rate. The contribution of renal excretion to total clearance from the systemic circulation (R) was estimated by subjecting oral clearance and creatinine clearance to regression in subjects with normal and impaired renal function. BA was estimated as f/R and compared with the observed BA (BA). The predicted BA values for 9 drugs fell within ±20% of their BA. The examined approach makes it possible to estimate BA values for drugs with mean renal excretion values in healthy subjects and oral clearance in subjects with various renal function, without intravenous pharmacokinetic data.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.dmpk.2021.100392 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A prospective study to evaluate high dose daptomycin pharmacokinetics and pharmacodynamics in spp. infective endocarditis.
Ther Adv Infect Dis
January 2025
Clinica di Malattie Infettive, Fondazione IRCCS Policlinico San Matteo, Pavia 27100, Italy.
Background: Daptomycin pharmacokinetics and pharmacodynamics data relative to higher doses in patients are necessary for clinical practice.
Objectives: A monocentric, prospective study that enrolled patients with a diagnosis of spp. infective endocarditis treated with daptomycin according to clinical practice, to evaluate the pharmacokinetics/pharmacodynamics of different daptomycin daily doses (group A: 8-10 and group B: 11-12 mg/kg).
A phase Ia study of a novel anti-HER2 antibody-drug conjugate GQ1001 in patients with previously treated HER2 positive advanced solid tumors.
J Transl Med
January 2025
Scientia Clinical Research and Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, 2052, Australia.
Background: A novel anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate (ADC) GQ1001 was assessed in patients with previously treated HER2 positive advanced solid tumors in a global multi-center phase Ia dose escalation trial.
Methods: In this phase Ia trial, a modified 3 + 3 study design was adopted during dose escalation phase. Eligible patients were enrolled, and GQ1001 monotherapy was administered intravenously every 3 weeks.
Meta-Analysis of the Input and Disposition of Various Dosage Forms of Methylprednisolone in Healthy Subjects Utilizing a Physiologically Based Pharmacokinetic Model.
AAPS J
January 2025
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, 160 Hayes Rd, Buffalo, New York, 14214, USA.
The study quantitatively analyzes and compares the pharmacokinetics (PK) of methylprednisolone (MPL) in humans upon administration of various dosage forms. The PK parameters and profiles of MPL in healthy subjects were collected from 22 literature sources. A minimal physiologically based pharmacokinetic (mPBPK) model consisting of blood and two tissue (lumped liver and kidney, remainder) compartments with nonlinear tissue partitioning was applied to describe MPL disposition.
View Article and Find Full Text PDFClaudin 18.2-targeting antibody-drug conjugate CMG901 in patients with advanced gastric or gastro-oesophageal junction cancer (KYM901): a multicentre, open-label, single-arm, phase 1 trial.
Lancet Oncol
January 2025
Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, China. Electronic address:
Background: CMG901 is a novel first-in-class antibody-drug conjugate with a humanised anticlaudin 18.2 antibody linked to microtubule-disrupting agent monomethyl auristatin E. We aimed to assess the antitumour activity and safety of CMG901 in patients with advanced gastric or gastro-oesophageal junction cancer and other solid tumours.
View Article and Find Full Text PDFA simple LC-MS/MS assay for the quantification of E6011, a novel anti-fractalkine monoclonal antibody, in cynomolgus monkey serum - comparison with ligand binding assay.
J Pharm Biomed Anal
December 2024
Global Drug Metabolism and Pharmacokinetics, Eisai Co., Ltd., Tokodai 5-1-3, Tsukuba-shi, Ibaraki 300-2635, Japan; Laboratory of Genomics-based Drug Discovery, Faculty of Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. Electronic address:
E6011 is a monoclonal antibody that is currently under development for the treatment of rheumatoid arthritis. While ligand binding assays (LBAs) are typically employed for the determination of therapeutic antibodies, ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) represents an alternative platform. E6011 in monkey serum was treated with ammonium sulfate to obtain pellets for subsequent processing.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!