Tavaborole, sold under the brand name Kerydin, is a topical antifungal medication for the treatment of onychomycosis, a fungal infection of the nail and nail bed with a complete clearance rate of 6-7% and partial clearance rate of 23-24% in individuals whose “infection border does not reach the cuticle at the base of the large toenail.” Tavaborole was approved by the US FDA in July 2014. The medication inhibits an essential fungal enzyme, leucyl-tRNA synthetase, that is required for protein synthesis. The inhibition of protein synthesis leads to termination of cell growth and then cell death, eliminating the fungal infection. Medical uses
Tavaborole is used in the treatment of onychomycosis. In clinical trials, tavaborole was more effective than the vehicle (ethyl acetate and propylene glycol) alone in curing onychomycosis. In two studies, fungal infection was eliminated using tavaborole in 6.5% of the cases vs. 0.5% using the vehicle alone, and 27.5% vs. 14.6% using the vehicle alone. Side effects
Application site exfoliation, erythema (rash), and irritation are possible side effects, and may occur in less than 5% of individuals. Pharmacology
Tavaborole acts as an inhibitor of fungal leucyl-tRNA synthetase. Pharmacokinetics
Tavaborole, when prepared with a 1:1 mixture of ethyl acetate and propylene glycol, has the ability to fully penetrate through the human nail. In studies with cadaver fingernails, a 5% solution of tavaborole penetrated the nail an average of 524.7 mcg/cm2 after two weeks of daily use.Tavaborole is detectable in the blood at a level of 3.54 ng/mL after a single use of 0.2 mL of the 5% solution.
In the same year Jabs et al. reported a family that over two generations had granulomatous synovitis, uveitis and cranial neuropathies. The condition was transmitted in an autosomal dominant fashion.Then in 1990 Pastores et al. reported a kindred with a phenotype very similar to what Blau described and suggested that the condition be called Blau Syndrome (BS). They also pointed out the similarities in the families noted above to BS but also pointed out the significant differences in the phenotypes.In 1996 Tromp et al. conducted a genome wide search using affected and non affected members of the original family. A marker, D16S298, gave a maximum logarithm of odds (LOD) score of 3.75 and put the BS susceptibility locus within the 16p12-q21 interval. Hugot et al. found a susceptibility locus for Crohn disease, a granulomatous inflammation of the bowel, on chromosome 16 close to the locus for BS. Based on the above information Blau suggested in 1998 that the genetic defect in BS and Crohn Disease might be the same or similar. Finally in 2001 Miceli-Richard et al. found the defect in BS to be in the nucleotide-binding domain of CARD15/NOD2. They commented in their article that mutations in CARD15 had also been found in Crohns disease. Confirmation of the defect in BS being in the CARD15 gene was made by Wang et al. in 2002 using the BS family and others.