The Effect of Ketoconazole on Whole Blood and Skin Ciclosporin Concentrations in Dogs

Section: Discussionsupporting

confidence: 92%

Therapeutic effectiveness of calcineurin inhibitors in canine vesicular cutaneous lupus erythematosus

Banović

Robson²,

Линек

et al. 2017

“…Oral administration of KETO has been shown substantially to reduce the oral CsA dose needed to maintain therapeutic blood levels in healthy dogs and, as a result, is used concurrently with CsA to make CsA an economically viable option for some clients. A recent study showed no difference in blood and skin CsA concentrations when CsA was dosed alone at 5.0 mg/kg once daily or at 2.5 mg/kg once daily with 2.5 mg/kg of KETO once daily . Another imidazole antifungal medication, FLU, has been shown, at multiple therapeutic doses, but not single or multiple subtherapeutic doses, possibly to increase the oral bioavailability of CsA in dogs .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of azithromycin in systemic and toothpaste forms for the treatment of ciclosporin‐associated gingival overgrowth in dogs

Rosenberg¹,

Rosenkrantz²,

Griffin³

et al. 2013

“…Ciclosporin A (Sigma‐Aldrich; St Louis, MO, USA) was diluted with DMSO and RPMI media; final concentration per well was 200 ng/mL. Target trough ciclosporin blood levels in dogs vary widely depending on the method and sample tested, and range from 100 to 600 ng/mL . A ciclosporin concentration of 200 ng/mL for PBMC in media and serum modulated canine PBMCs cytokine responses and was postulated to be comparable to therapeutic levels in vivo .…”

Section: Methodsmentioning

confidence: 99%

Immunomodulatory in vitro effects of oclacitinib on canine T‐cell proliferation and cytokine production

Banović

Tarigo

Gordon

et al. 2018

Background Oclacitinib is a Janus kinase inhibitor used to control pruritus and skin lesions in canine allergic skin disease; its effect on canine T cells is not well‐characterized. Hypothesis/Objectives To evaluate the impact of oclacitinib on cultured T cells using peripheral blood mononuclear cells from dogs. Animals Six bluetick coonhounds. Methods and materials Lymphocyte‐enriched cells were incubated with or without the T‐cell mitogen concanavalin A (Con A), oclacitinib (0.5, 1 or 10 μM), ciclosporin (200 ng/mL), Con A + oclacitinib 1 μM and Con A + ciclosporin. We assessed both T‐cell proliferation and the secretion of cytokines. Results Ciclosporin and oclacitinib both inhibited the spontaneous proliferation of T cells; this effect was significant only after incubation with oclacitinib at 10 μM. At this concentration, oclacitinib significantly reduced the spontaneous secretion of clonal activator cytokines [interleukin (IL)‐2, IL‐15], pro‐inflammatory cytokines (interferon‐gamma (IFN‐γ), IL‐18) and the regulatory cytokine IL‐10; tumour necrosis factor alpha (TNF‐α) and IL‐6 cytokine production was mildly inhibited. After Con A stimulation, only T cells co‐treated with ciclosporin achieved a significant proliferation inhibition and reduction of IL‐2, IL‐10, IL‐15, IL‐18, IFN‐γ and TNF‐α. Surprisingly, oclacitinib at 1 μM (337 ng/mL, corresponding to the oral dosage of 0.4–0.6 mg/kg) did not significantly affect Con A‐stimulated T‐cell proliferation nor cytokine production (IL‐2, IL‐10, IL‐15, IL‐18, IFN‐γ and TNF‐α). Conclusions Although a limited number of dogs were investigated, these preliminary results suggest that oclacitinib appears to have immunosuppressive properties, but only at dosages above those used to treat allergic pruritus in dogs.