Role of the N-acetylation polymorphism in solithromycin metabolism.

Abstract

AIM:

Solithromycin is a new macrolide antibiotic for the potential treatment of bacterial pneumonia.

MATERIALS & METHODS:

Solithromycin N-acetylation by human NAT1 and NAT2 was investigated following recombinant expression in yeast and in cryopreserved human hepatocytes from rapid, intermediate and slow acetylators.

RESULTS:

Solithromycin exhibited over twofold higher affinity for recombinant human NAT2 than NAT1. Apparent maximum velocities for the N-acetylation of solithromycin catalyzed by the NAT2 allozyme associated with rapid acetylators were significantly (p < 0.01) higher than by the NAT2 allozymes associated with slow acetylators. Robust gene dose responses (rapid>intermediate>slow acetylators) were exhibited in cryopreserved human hepatocytes in situ following incubation with 100 μM solithromycin.

CONCLUSION:

Solithromycin is N-acetylated by human NAT1 and NAT2 and the role of the NAT2 acetylation polymorphism on solithromycin metabolism may be concentration dependent.

• Authors: David W Hein, Mark A Doll
• Journal: Pharmacogenomics (Pharmacogenomics) Vol. 18 Issue 8 Pg. 765-772 (Jun 2017) ISSN: 1744-8042 [Electronic] England
• PMID: 28625123 (Publication Type: Journal Article)

Chemical References

• Isoenzymes
• Macrolides
• Triazoles
• solithromycin
• Arylamine N-Acetyltransferase

Topics

• Acetylation
• Arylamine N-Acetyltransferase (genetics, metabolism)
• Hepatocytes (metabolism)
• Humans
• Isoenzymes (genetics, metabolism)
• Macrolides (metabolism)
• Polymorphism, Genetic (genetics)
• Triazoles (metabolism)