サレサイクリン

Compared to various examples of first-line tetracycline therapies for moderate to severe acne like doxycycline and minocycline, studies have shown that sarecycline can be sixteen to thirty-two fold less active against aerobic Gram-negative bacilli present within the normal human intestinal microbiome. Furthermore, it has also been demonstrated that sarecycline may be four to eight fold less active against various anaerobic bacteria that also comprise the normal human intestinal microbiome. Subsequently, while doxycycline and minocycline typically elicit broad-spectrum antimicrobial activity that can often cause adverse effects like diarrhea, fungal overgrowth, vaginal candidiasis, etc. due to undesirable off-target antibacterial effects on endogenous intestinal flora, sarecycline demonstrates a noticeably more target specific narrow spectrum activity with lower incidence of such side effects. Moreover, sarecycline also shares a relatively low propensity for resistance development in Cutibacterium acnes - one of the principal anaerobic organisms associated with acne lesions - with doxycycline and minocycline treatments.

It has been demonstrated that tetracyclines like sarecycline elicit their antimicrobial action by targeting and inhibiting protein synthesis in microbial agents like Cutibacterium acnes present in acne lesions. In particular, it is believed that sarecycline's mechanism of action revolves around the inhibition of various macromolecular biosynthesis activities like the macromolecular biosynthesis of microbial DNA, RNA, proteins, lipids, and cell wall. Specifically, it has been observed that while sarecycline demonstrates appreciable inhibition of microbial macromolecular DNA and protein synthesis, the compound has little to no effect on lipid biosynthesis, cell wall synthesis, and RNA synthesis. In addition, because Cutibacterium acnes also generates proteins and enzymes that are capable of causing inflammation, it is also believed that tetracyclines like sarecyclines can also affect an anti-inflammatory effect via the inhibition of such microbial protein synthesis.

The median time to peak plasma concentration (Tmax) of sarecycline is 1.5 to 2.0 hours. When the medication is taken with a meal consisting of high fat (about 50% of total caloric content of the meal), high caloric (about 800 to 1000 Kcal), and milk content the Tmax can be delayed by approximately 0.53 hours and the Cmax and AUC can be decreased by 31% and 27%, respectively.

After a single 100 mg oral dose of radiolabeled sarecycline, 42.6% of the dose was recovered in feces (14.9% as unchanged) and 44.1% in urine (24.7% as unchanged).

The mean apparent volume of distribution of sarecycline at steady-state ranges from 91.4 L to 97.0 L.

The mean apparent oral clearance (CL/F) of sarecycline at steady state is about 3 L/h.