Journal
JOURNAL OF PHARMACOLOGICAL SCIENCES
Volume 113, Issue 4, Pages 315-324Publisher
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1254/jphs.10109FP
Keywords
azithromycin; erythromycin; clarithromycin; P-glycoprotein; Caco-2
Categories
Funding
- GlaxoSmithKline Australia
- Novartis Pharma, Basel, Switzerland [PSC-833]
Ask authors/readers for more resources
This study was conducted to determine the rate of P-glycoprotein (P-gp)-mediated efflux of digoxin analogues and metabolites and to assess the effects of macrolide antibiotics on this efflux. Bidirectional transport studies were conducted using our Caco-2 sub clone with high P-gp expression (CLEFF9). HPLC methods were employed to measure drug transport. All digoxin metabolites were P-gp substrates, although digoxin had the greatest efflux ratio. Erythromycin had no effect on the transport of digoxin, maintaining a basolateral to apical efflux ratio of 14.8, although it did reduce the efflux ratio of dihydrodigoxin and digoxigenin by 34% and 43%, respectively. Azithromycin also had little effect on the transport of digoxin or any of its metabolites. in contrast, clarithromycin and roxithromycin almost eliminated basolateral targeted efflux. Using paclitaxel as a known P-gp substrate, erythromycin demonstrated only partial P-gp inhibitory capacity, maintaining an efflux ratio over 100. In contrast, clarithromycin and roxithromycin were 10-fold greater P-gp-inhibitors. Clarithromycin and roxithromycin are likely to exhibit drug interactions with digoxin via inhibition of efflux mechanisms. Azithromycin appears to have little influence on P-gp mediated digoxin absorption or excretion and would be the safest macrolide to use concurrently with oral digoxin.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available