title: Pharmacokinetics of macrolactin A and 7-O-succinyl macrolactin A in mice.
abstract: 1.  As promising anti-macular degeneration and/or anti-tumour agents, a better understanding of the pharmacokinetics of macrolactin A (MA) and 7-O-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. 2.  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 (Vss) in mice. A relatively slower CL (by 54.1%) and smaller Vss (by 85.8%) were observed for SMA than for MA. In accordance with the larger Vss values of MA than of SMA, the mouse tissues studied had good affinity to MA but less affinity to SMA. 3.  Both MA and SMA had an extremely low oral extent of absolute bioavailability (F). 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. 4.  The pharmacokinetic profiles of both MA and SMA were much improved (greater AUC and F values) following intraperitoneal administration than following oral administration due to avoidance of acidic degradation and/or gastrointestinal first-pass extraction.
authors.affiliation: College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea , Bucheon, Gyeonggi-Do , South Korea and.
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Jung
authors.forename: Ju Myung
authors.initials: JM
authors.lastname: Kim
authors.forename: Mi Hye
authors.initials: MH
authors.lastname: Kwon
authors.forename: Dong Hee
authors.initials: DH
authors.lastname: Kim
authors.forename: Hee Eun
authors.initials: HE
authors.lastname: Kang
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D006801:Humans; D007274:Injections, Intraperitoneal; D018942:Macrolides / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008813:Mice, Inbred ICR; D051381:Rats; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: C559723:7-O-succinyl macrolactin A; D018942:Macrolides; C453562:macrolactin A