ABSTRACT
Infections caused by Penicillium species are rare in dogs, and the prognosis in these cases is poor. An unknown species of Penicillium was isolated from a bone lesion in a young dog with osteomyelitis of the right ilium. Extensive diagnostic evaluation did not reveal evidence of dissemination. Resolution of lameness and clinical stability of disease were achieved with intravenous phospholipid-complexed amphotericin B initially, followed by long-term combination therapy with terbinafine and ketoconazole. A detailed morphological and molecular characterization of the mold was undertaken. Sequence analysis of the internal transcribed spacer revealed the isolate to be closely related to Penicillium menonorum and Penicillium pimiteouiense. Additional sequence analysis of ß-tubulin, calmodulin, minichromosome maintenance factor, DNA-dependent RNA polymerase, and pre-rRNA processing protein revealed the isolate to be a novel species; the name Penicillium canis sp. nov. is proposed. Morphologically, smooth, ovoid conidia, a greenish gray colony color, slow growth on all media, and a failure to form ascomata distinguish this species from closely related Penicillium species.
Subject(s)
Dog Diseases/microbiology , Osteomyelitis/veterinary , Penicillium/classification , Penicillium/isolation & purification , Amphotericin B/therapeutic use , Animals , Antifungal Agents/therapeutic use , Cluster Analysis , DNA, Fungal/chemistry , DNA, Fungal/genetics , DNA, Ribosomal Spacer/chemistry , DNA, Ribosomal Spacer/genetics , Dog Diseases/drug therapy , Dogs , Female , Fungal Proteins/genetics , Histocytochemistry , Ketoconazole/therapeutic use , Molecular Sequence Data , Naphthalenes/therapeutic use , Osteomyelitis/drug therapy , Osteomyelitis/microbiology , Penicillium/genetics , Phylogeny , Radiography, Abdominal , Sequence Analysis, DNA , Terbinafine , Treatment OutcomeABSTRACT
BACKGROUND: Gefitinib (IRESSA) is normally administered as a once-daily oral tablet. However, many patients with head and neck cancer have difficulty swallowing medication in a tablet form. A granular formulation has recently been developed to facilitate the administration of gefitinib to patients who are unable to swallow tablets. OBJECTIVES: The aims of this study were to determine the relative bioavailability of a single dose of gefitinib when administered as 250 mg of a new granular formulation compared with the standard 250 mg tablet, and to assess the intra-subject variability of the granular formulation, in healthy subjects. METHODS: This was a randomized, open-label, three-period crossover study. Healthy male subjects (n = 18) received either a single gefitinib 250 mg tablet (once), or a 250 mg granular formulation of gefitinib (on two separate occasions) over the three dosing periods, in randomized order. Plasma concentrations of gefitinib were measured up to 240 h post-dose. RESULTS: The treatment ratio estimates for area under the plasma concentration versus time curve (AUC) and peak plasma concentration (C (max)) for the granular formulation when compared with the tablet were 1.05 (90% confidence intervals [CI] for the ratio 0.97-1.13) and 1.14 (90% CI for the ratio 1.01-1.28), respectively. The estimate for the intra-subject standard deviation for the granular formulation when given on 2 separate occasions was 0.143 for AUC and 0.165 for C (max), equivalent to a 1.4- and 1.7-fold intra-subject variability in AUC and C (max), compared with that observed for the tablet of two and threefold, respectively. CONCLUSIONS: There was little difference in exposure to gefitinib administered as the 250 mg granular formulation compared with the 250 mg standard tablet. The granular formulation of gefitinib could provide an alternative treatment regimen for patients unable or unwilling to swallow the standard tablet formulation, without compromizing exposure to gefitinib.