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 (V_ss) in mice. A relatively slower CL (by 54.1%) and smaller V_ss (by 85.8%) were observed for SMA than for MA. In accordance with the larger V_ss 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.

• 7-O-succinyl macrolactin A
• macrolactin A
• mouse
• pharmacokinetics
• tissue distribution

Acknowledgements

This study was supported by part by the contract, “Pharmacokinetic Study of Macrolactin A and 7-O-Succinyl Macrolactin A” from Daewoo Pharmaceutical Company Ltd., Busan, South Korea and in part by the Research Fund (M-2012-B0002-00031), 2012 of The Catholic University of Korea.