Metabolism and disposition of the oral absorption enhancer 14C-radiolabeled 8-(N-2-hydroxy-5-chlorobenzoyl)-amino-caprylic acid (5-CNAC) in healthy postmenopausal women and supplementary investigations in vitro

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Hans-Peter GschwindM Azria

Abstract

8-(N-2-hydroxy-5-chlorobenzoyl)-amino-caprylic acid (5-CNAC), a compound lacking pharmacological activity enhances the absorption of salmon calcitonin, when co-administered. Disposition and biotransformation of 5-CNAC was studied in six healthy postmenopausal women following a single oral dose of 200mg (14)C-radiolabeled 5-CNAC (as disodium monohydrate salt). Blood, plasma, urine and feces collected over 7 days were analyzed for radioactivity. Metabolite profiles were determined in plasma and excreta and metabolite structures were elucidated by LC-MS/MS, LC-(1)H NMR, enzymatic methods and by comparison with reference compounds. Oral 5-CNAC was safe and well tolerated in this study population. 5-CNAC absorption was rapid (t(max)=0.5h; C(max)=9.00 ± 2.74 μM (mean ± SD, n=6) and almost complete. The elimination half-life (t(½)) was 1.5 ± 1.1h. The radioactive dose was excreted mainly in urine (≥ 90%) in form of metabolites and 0.071% as intact 5-CNAC. Excretion of radioactivity in feces was minor and mostly as metabolites (<3%). Radioactivity in plasma reached C(max) (35.4 ± 7.9 μM) at 0.75 h and declined with a half-life of 13.9 ± 4.3h. 5-CNAC accounted for 5.8% of the plasma radioactivity AUC(0-24h). 5-CNAC was rapidly cleared f...Continue Reading

References

Jan 1, 1992·The Journal of Clinical Endocrinology and Metabolism·B E NordinM Horowitz
Jan 1, 1989·European Journal of Clinical Pharmacology·T HoriuchiT Hata
Dec 1, 1987·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·J C GallagherA Moy
Oct 13, 1995·Journal of Medicinal Chemistry·A Leone-BayH Leipold
Feb 2, 1995·The New England Journal of Medicine·S C Manolagas, R L Jilka
Dec 1, 1995·Calcified Tissue International·M AzriaJ M Zanelli
Aug 7, 2002·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Thierry BuclinMartine Attinger
Aug 18, 2004·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·László B TankóClaus Christiansen
Jul 12, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Hans-Peter GschwindGerhard Gross
Nov 25, 2005·Current Drug Delivery·Dmitry MalkovIsabel Gomez-Orellana
Aug 3, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Lorenz M JostDirk Laurent
Apr 18, 2009·British Journal of Clinical Pharmacology·Morten A KarsdalClaus Christiansen

❮ Previous
Next ❯

Citations

Sep 17, 2013·Journal of Pharmaceutical and Biomedical Analysis·Shuoye YangXijing Chen
Jul 1, 2016·Tissue Barriers·Fiona McCartneyDavid J Brayden
Dec 19, 2019·Nature Reviews. Drug Discovery·Daniel J Drucker
Aug 22, 2021·Advanced Drug Delivery Reviews·Sam Maher, David J Brayden

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.