Sarecycline API Manufacturers

General Description:

Sarecycline, identified by CAS number 1035654-66-0, is a notable compound with significant therapeutic applications. Sarecycline is a semi-synthetic derivative of tetracycline that was initially discovered by Paratek Pharmaceuticals from Boston, MA but then licensed to Warner Chilcott of Rockaway, NJ in July of 2007 . After completing various phase-II and phase-III trials demonstrating its effectiveness in treating moderate to severe facial acne vulgaris the US Food and Drug Administration approved Barcelona based Almirall, S.A.'s Seysara (sarecylcine) as a new first in class narrow spectrum tetracycline derived oral antibiotic for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients nine years of age and older . Seysara (sarecycline) was originally part of Allergan's US Medical Dermatology portfolio, before Almirall acquired the portfolio in the second half of 2018 as a means of consolidating and reinforcing the dermatology-focused pharmaceutical company's presence in the United States . Acne vulgaris itself is a common chronic skin condition associated with the blockage and/or inflammation of hair follicles and their accompanying sebaceous glands . The acne often presents physically as a mixture of non-inflammatory and inflammatory lesions mainly on the face but on the back and chest as well . Based upon data from Global Burden of Disease studies, the acne vulgaris condition affects up to 85% of young adults aged 12 to 25 years globally - with the possibility of permanent physical and mental scarring resulting from cases of severe acne . Subsequently, while a number of first line tetracycline therapies like doxycycline and minocycline do exist for treating acne vulgaris, sarecycline presents a new and innovative therapy choice because it exhibits the necessary antibacterial activity against relevant pathogens that cause acne vulgaris but also possesses a low propensity for resistance development in such pathogens and a narrower, more specific spectrum of antibacterial activity, resulting in fewer off-target antibacterial effects on endogenous intestinal flora and consequently fewer resultant adverse effects associated with diarrhea, fungal overgrowth, etc.

Indications:

This drug is primarily indicated for: Sarecycline is a tetracycline-class drug indicated for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 9 years of age and older . Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Sarecycline undergoes metabolic processing primarily in: Metabolism of sarecycline by enzymes in human liver microsomes is minimal (< 15%) in vitro . Minor metabolites resulting from non-enzymic epimerization, O-/N-demethylation, hydroxylation, and desaturation have been found . This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Sarecycline are crucial for its therapeutic efficacy: 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 . The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Sarecycline is an important consideration for its dosing schedule: The mean elimination half-life of sarecycline is 21 to 22 hours . This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Sarecycline exhibits a strong affinity for binding with plasma proteins: The protein binding of sarecycline has been recorded as ranging from 62.5% to 74.7% in vitro . This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Sarecycline from the body primarily occurs through: 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) . Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Sarecycline is distributed throughout the body with a volume of distribution of: The mean apparent volume of distribution of sarecycline at steady-state ranges from 91.4 L to 97.0 L . This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Sarecycline is a critical factor in determining its safe and effective dosage: The mean apparent oral clearance (CL/F) of sarecycline at steady state is about 3 L/h . It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Sarecycline exerts its therapeutic effects through: 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 . The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Sarecycline functions by: 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 . This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Sarecycline belongs to the class of organic compounds known as tetracyclines. These are polyketides having an octahydrotetracene-2-carboxamide skeleton, substituted with many hydroxy and other groups, classified under the direct parent group Tetracyclines. This compound is a part of the Organic compounds, falling under the Phenylpropanoids and polyketides superclass, and categorized within the Tetracyclines class, specifically within the None subclass.

Categories:

Sarecycline is categorized under the following therapeutic classes: Anti-Acne Preparations, Anti-Acne Preparations for Systemic Use, Anti-Bacterial Agents, Anti-Infective Agents, Antibacterials for Systemic Use, Antiinfectives for Systemic Use, Dermatologicals, Naphthacenes, P-glycoprotein inhibitors, Tetracyclines. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.