Posaconazole (Noxafil®, Schering Corp., Kenilworth, NJ 07033) is a potent, broad-spectrum triazole anti-fungal agent used to treat aggressive infections caused by a variety of fungal organisms to include those responsible for aspergillosis, fusariosis, zygomycosis, candidiasis, and coccidioidomycosis. Its use in marine mammal medicine is of particular interest for the treatment of zygomycosis in cetaceans. A confirmed case of Apophysomyces elegans in a 5 week old orphaned bottlenose dolphin (Tursiops truncatus) has been successfully treated with Posaconazole in Panama City Beach, Florida. The drug has since been used on several confirmed or suspected cases of zygomycosis. SeaWorld San Antonio currently has a 5 year old male Pacific white-sided dolphin (Lagenorhynchus obliquidens) undergoing treatment with posaconazole for a suspected case of zygomycosis. Clinical history, hematology, and serum chemistries were very similar to previously confirmed cases of the disease.
We used the same protocol previously used with success, that being 5 mg/kg twice a day of the oral suspension injected into fish which are then fed to the animal. Duration of treatment is subjective at best. We have elected to continue treatment in this case for 18 months. To make our dosage with posaconazole objective rather than subjective, serum levels were determined on the Lagenorhynchus and compared to a Tursiops truncatus treated in Fort Walton Beach, Florida. The serum level at 24 hours was 2.24 µg/ml. At 134 days, it was 4.26 µg/ml, and at 252 days, the serum level had risen to 5.09 µg/ml. Serum levels documented in the Tursiops in Fort Walton Beach after 49 days of treatment and 7 days after discontinuing were 5.25 µg/ml and 1.49 µg/ml, respectively.
In human studies, the maximum concentrations of posaconazole are achieved at 5.8 - 8.8 hours after a single oral dose. Steady state levels are reached within 10 days of twice daily dosing. Serum levels were equal to or lower for dosages above 800 mg/day indication possible saturation of absorption above 800 mg. In an in vitro study, posaconazole had an overall minimum inhibitory concentration at the 90% level of 1 µg/ml against 36 isolates of Zygomycetes.1
Our goals are to determine therapeutic levels of posaconazole in cetaceans and to measure serum levels after discontinuing treatment. More data will become available through future clinical trials.
The authors wish to thank the laboratory staff at SeaWorld San Antonio for their patience with us and for insuring the samples were run in a timely manner.
1. Dannaoui E., J. Meletiadis, J.W. Mouton, J.F. Meis, and P.E. Verweij. 2003. In vitro susceptibilities of zygomycetes to conventional and new antifungals. J Antimicrob Chemother 51: 45-52.