Oral pharmacokinetic and pharmacodynamic effects of FTY720 in cats.
The aim of the study was to determine pharmacokinetic and pharmacodynamic profiles of FTY720 in cats and identify any toxic side effects. Six adult cats were used for the experimental study. Single oral dosages were tested at 0.05, 0.3 and 1.0 mg/kg. Whole blood drug concentration, total white blood cell and differential counts were monitored. Flow cytometry evaluated the effects on lymphocyte subsets. A toxicity study consisted of cats receiving a dose of 0.15 mg/kg daily for 30 days. Daily observation, physical examination and bloodwork were evaluated to assess for toxicity. All single doses resulted in > or =80% reduction in circulating lymphocytes within 12 h after administration, with the duration of lymphopenia being dose dependent. CD4+ and CD5+ T cells were specifically depleted. Peripheral neutrophils declined by approximately 70% at all dosages tested. No other toxic side effects were observed. Results of this study suggest that FTY720 is effective at inducing a peripheral lymphopenia in cats without any toxic side effects. Currently, cats appear to be the only species in which FTY720 induces a neutropenia. This study provides the foundation for future clinical transplantation trials using FTY720 in cats. By using combination therapy of FTY720 and low dose cyclosporine, the incidence of serious side effects may be reduced while still preventing allograft rejection.
Downes
S
S
Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616-8745, USA.
Chen
Y-J
YJ
Kyles
A
A
Gregory
C
C
D000284:Administration, Oral; D000818:Animals; D001772:Blood Cell Count / Q000662:veterinary; D002415:Cats / Q000378:metabolism*; D000068876:Fingolimod Hydrochloride; D005434:Flow Cytometry / Q000662:veterinary; D007155:Immunologic Factors / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D016131:Lymphocyte Subsets / Q000187:drug effects*; D008297:Male; D011409:Propylene Glycols / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology
D007155:Immunologic Factors; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine