Pharmacokinetics of macrolactin A and 7-O-succinyl macrolactin A in mice. (June 2014)

• Record Type: Journal Article
• Authors: Jung, Ji Won; Kim, Ju Myung; Kwon, Mi Hye; Kim, Dong Hee; Kang, Hee Eun
• Is Part Of: Xenobiotica. Volume 44:Number 6(2014:Jun.)
• Page Start: 547
• Page End: 554
• Publication Date: 2014-06
• Subjects: Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.3109/00498254.2013.861542
• Languages: English
• ISSNs: 0049-8254

Abstract

<abstract> <title>Abstract</title> <p>1. <?ri?>As promising anti-macular degeneration and/or anti-tumour agents, a better understanding of the pharmacokinetics of macrolactin A (MA) and 7-<italic>O</italic>-succinyl macrolactin A (SMA) is essential. Thus, we evaluated the pharmacokinetics of MA and SMA after intravenous, oral, or intraperitoneal administration of each drug to mice.</p> <p>2. <?ri?>Both hepatic and extra-hepatic extractions of MA were expected based on the rapid total body clearance (CL) of MA. MA also showed a large steady-state volume of distribution (<italic>V</italic><sub>ss</sub>) in mice. A relatively slower CL (by 54.1%) and smaller <italic>V</italic><sub>ss</sub> (by 85.8%) were observed for SMA than for MA. In accordance with the larger <italic>V</italic><sub>ss</sub> values of MA than of SMA, the mouse tissues studied had good affinity to MA but less affinity to SMA.</p> <p>3. <?ri?>Both MA and SMA had an extremely low oral extent of absolute bioavailability (<italic>F</italic>). This could have been a result of the instability of MA and SMA in the gastrointestinal tract, supported by their unstable property in acidic buffer. Gastrointestinal and/or hepatic first-pass extraction of MA and SMA may be other reasons.</p> <p>4. <?ri?>The pharmacokinetic profiles of both MA and SMA were much improved (greater AUC and <italic>F</italic> values) following intraperitoneal administration than following oral administration due to avoidance of acidic degradation and/or gastrointestinal first-pass extraction.</p> </abstract>