Tavaborole (AN-2690) exhibits an 8-fold rise in activity against Aspergillus fumigatus and an 8-fold increase against Cryptosporidium neoformans [1]. Tavaborole (AN-2690) has little effect on cells expressing GlLeuRS or GlLeuRS-D444E, but it severely inhibits cells expressing GlLeuRS-D444A [2].

Absorption, Distribution and Excretion
7.5%. Subungual onychomycosis is difficult to treat because the infection site is located in the nail bed, which has poor blood supply. Effective topical treatment must penetrate the nail plate and reach the infection site at a concentration sufficient to exert antifungal activity. Studies have shown that tavaborone produces antifungal activity after 5 days of topical application. It is primarily excreted via the kidneys. This study investigated the pharmacokinetics of tavaborone in 24 subjects with distal subungual onychomycosis (involving at least 4 toenails, including at least 1 big toenail). Subjects received a single dose followed by daily topical application of 200 μL of 5% tavaborone solution to all 10 toenails and the surrounding 2 mm of skin for 2 weeks. Steady-state was reached after 14 days of treatment. Following a single dose, the mean peak concentration (Cmax) of tavaborone (± standard deviation) was 3.54 ± 2.26 ng/mL (n=21, measurable concentration, range 0.618–10.2 ng/mL, limit of quantitation (LLOQ) = 0.5 ng/mL), and the mean AUC_last was 44.4 ± 25.5 nghr/mL (n=21). After two weeks of daily administration, the mean Cmax was 5.17 ± 3.47 ng/mL (n=24, range 1.51–12.8 ng/mL), and the mean AUC_t was 75.8 ± 44.5 nghr/mL. Renal excretion is the primary clearance route. In a clinical pharmacology trial involving six healthy adult male volunteers, subjects received a single topical application of 5% (14)C-tavaborone solution, and the results showed that tavaborone conjugates and metabolites were primarily excreted in the urine.
/Milk/ It is unclear whether tavaborone is secreted into human breast milk after topical application of Kerydin.
Onychomycosis is a common nail infection that causes thickening and discoloration of the nails. The appearance of infected nails can affect a patient's self-image and negatively impact their quality of life. Patients may use nail polish to cover the appearance of infected nails. /The purpose of this study/ To evaluate the in vitro permeation characteristics of a 5% tavaborone topical solution through nail polish using excised, disease-free human fingernails. In Study 1, tavaborone permeation was assessed during a 20-day administration period using Franz limiting-dose technology and a modified Franz diffusion cell. Nails were either coated with one layer of over-the-counter (OTC) regular nail polish or left uncoated (control group). In Study 2, tavaborone permeation was measured during a 14-day administration period using limiting-dose technology and a vertical diffusion cell. Nails were either coated with one or four layers of salon-grade nail polish, or two or one layers of OTC regular nail polish, or left uncoated. In Study 1, the mean cumulative penetration ± standard deviation (SD) of tavaborone on day 21 was numerically higher than that of unpainted nails (3,526 ± 1,433 μg/cm² vs. 2,661 ± 1,319 μg/cm²), but the difference was not statistically significant. In Study 2, the mean cumulative penetration of tavaborone in all polished nails was also higher than that in unpainted nails (statistical significance was not assessed). On day 15, the mean cumulative nail penetration (± standard deviation) of tavaborone was: 1179 ± 554 μg/cm² through 4 layers of salon-grade nail polish; 1227 ± 974 μg/cm² through 1 layer of salon-grade nail polish; 1493 ± 1322 μg/cm² through 2 layers of over-the-counter nail polish; 1428 ± 841 μg/cm² through 1 layer of over-the-counter nail polish; and 566 ± 318 μg/cm² through unpainted nails. These in vitro results indicate that tavaborone can penetrate human nails coated with four layers of nail polish.

---

Metabolism/Metabolites
Tavaborone undergoes extensive metabolism. Metabolite analysis showed extremely low levels of sulfate conjugates and benzoic acid metabolites, consistent with known tavaborone biotransformation.
Tavaborone has extensive metabolism. …In a clinical pharmacology trial involving six healthy adult male volunteers, a single topical application of 5% (14)C-tavaborone solution showed that tavaborone conjugates and metabolites were primarily excreted in the urine.

---

Biological half-life
28.5 hours

Toxicity Summary
Identification and Uses: Tavaborone is a white to off-white powder belonging to the oxorubane class of antifungal agents. Oxorubanes are boron-containing molecules with antifungal activity. A 5% tavaborone topical solution is indicated for the treatment of onychomycosis caused by Trichophyton rubrum or Trichophyton mentagrophytes. Human Exposure and Toxicity: A randomized, single-blind, controlled study involving 234 adults aged 18–75 years assessed the potential for sensitization with tavaborone. No evidence of sensitization was found. In another study, a 5% tavaborone solution, excipient solution, a positive irritation control (0.5% sodium dodecyl sulfate solution), and a negative irritation control (0.9% sodium chloride solution) were simultaneously applied to different areas of the back of 45 healthy adults aged 18–75 years once daily for 21 days. Local irritation symptoms were assessed 30 minutes after application. Data from days 2–22 showed that the mean irritation response to the 5% tavaborone solution was higher than that to the positive irritation control. In vitro genotoxicity assays (human lymphocyte chromosome aberration assay) showed that tavaborone did not exhibit mutagenic or chromosome breakage potential. Animal studies: Carcinogenicity of tavaborone was investigated via dermal and oral administration. In dermal administration studies, mice were topically treated once daily with 5%, 10%, and 15% tavaborone solutions for 104 weeks. No drug-related neoplasia was observed with topically applied tavaborone solutions at concentrations up to 15%. In oral administration studies, rats were given once-daily oral doses of tavaborone at doses of 12.5, 25, and 50 mg/kg/day for 104 weeks. No drug-related neoplasia was observed with oral doses up to 50 mg/kg/day. In a prenatal and postnatal developmental study in rats, oral doses of tavaborone were administered from the onset of organogenesis (day 6 of gestation) to the end of lactation (day 20 of lactation), at doses of 15, 60, and 100 mg/kg/day. With extremely low maternal toxicity, no embryotoxicity or effects on postnatal development were observed at a dose of 100 mg/kg/day. In a rabbit skin embryonic development study, 1%, 5%, and 10% tavaborone solutions were applied topically to pregnant female rabbits during organogenesis (days 6–28 of gestation). In the 5% and 10% tavaborone solutions, skin irritation at the treatment site increased in a dose-dependent manner. The 10% tavaborone solution resulted in decreased fetal weight. In the 10% tavaborone solution (based on AUC comparison, at a dose 36 times the maximum recommended human dose (MRHD)), no drug-related malformations were observed in rabbits. In the 5% tavaborone solution (based on AUC comparison, at a dose 26 times the maximum recommended human dose (MRHD)), no embryotoxicity was observed in rabbits. In early pregnancy and before pregnancy, no effects on fertility were observed in male and female rats treated with oral doses of up to 300 mg/kg/day of tavaborone (equivalent to 107 times the maximum recommended human dose based on AUC comparison). Results from in vitro genotoxicity studies (Ames test) and in vivo genotoxicity studies (rat micronucleus test) showed that tavaborone was not mutagenic or chromosomally breakable.

---

Effects during pregnancy and lactation
◉ Overview of use during lactation
No studies have been conducted on topical application of tavaborone during lactation. Due to the very low concentration of the drug in the blood after topical application to the nails, it is unlikely that measurable amounts of the drug will enter breast milk.
◉ Effects on breastfed infants
No published information found as of the revision date.
◉ Effects on lactation and breast milk
No published information found as of the revision date.

[1]. Discovery of a new boron-containing antifungal agent, 5-fluoro-1,3-dihydro-1-hydroxy-2,1- benzoxaborole (AN2690), for the potential treatment of onychomycosis. J Med Chem. 2006 Jul 27;49(15):4447-50.

[2]. Post-transfer editing by a eukaryotic leucyl-tRNA synthetase resistant to the broad-spectrum drug AN2690. Biochem J. 2010 Sep 1;430(2):325-33.

Therapeutic Uses

Antifungal Drugs
/Clinical Trials/ ClinicalTrials.gov is a registry and results database that lists human clinical studies funded by public and private institutions worldwide. The website is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each record on ClinicalTrials.gov includes a summary of the study protocol, including: the disease or condition; the intervention (e.g., the medical product, behavior, or procedure being studied); the title, description, and design of the study; participation requirements (eligibility criteria); the location of the study; contact information for the study location; and links to relevant information from other health websites, such as the NLM's MedlinePlus (for patient health information) and PubMed (for citations and abstracts of academic articles in the medical field). Tavaborone is included in the database.
Kerydin (tavaborone) 5% topical solution is an oxyborane antifungal drug indicated for the treatment of onychomycosis caused by Trichophyton rubrum or Trichophyton mentagrophytes. /US Product Label Contains/

---

Drug Warnings
Adverse reactions have been reported in at least 1% of adults treated with 5% tavaborone topical solution, and the incidence is higher than with excipient-based topical solutions. These include desquamation at the application site, ingrown nails, erythema at the application site, and dermatitis at the application site.
5% tavaborone topical solution may cause skin irritation; there is currently no evidence that this solution causes contact sensitization.
It is unknown whether tavaborone is excreted into human breast milk after topical application. Because many drugs are excreted into human breast milk, caution should be exercised when breastfeeding women take Kerydin.
There are currently no adequate and well-controlled studies of Kerydin in pregnant women. Kerydin should only be used during pregnancy if the potential benefit outweighs the potential risk to the fetus.
For more complete data on drug warnings for tavaborone (9 of 9), please visit the HSDB record page.

---

Pharmacodynamics
After a single dose, the mean peak concentration (Cmax) of tavaborone (± standard deviation) was 3.54 ± 2.26 ng/mL (n=21, measurable concentration, range 0.618–10.2 ng/mL, limit of quantitation (LLOQ) = 0.5 ng/mL), and the mean AUClast was 44.4 ± 25.5 nghr/mL (n=21). After 2 weeks of daily administration, the mean Cmax was 5.17 ± 3.47 ng/mL (n=24, range 1.51–12.8 ng/mL), and the mean AUCτ was 75.8 ± 44.5 nghr/mL.

C7H6BFO2

151.9307

152.044

174671-46-6

174671-46-6

11499245

White to off-white solid powder

1.3±0.1 g/cm3

230.8±50.0 °C at 760 mmHg

120-122 °C

93.4±30.1 °C

0.0±0.5 mmHg at 25°C

1.526

0.043

1

3

0

11

155

0

LFQDNHWZDQTITF-UHFFFAOYSA-N

InChI=1S/C7H6BFO2/c9-6-1-2-7-5(3-6)4-11-8(7)10/h1-3,10H,4H2

5-fluoro-1-hydroxy-3H-2,1-benzoxaborole

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~658.20 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (16.45 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (16.45 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (16.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)