Plasma itraconazole concentrations during treatment of feline sporotrichosis

Author:

Pereira-Oliveira Gabriela Reis1ORCID,Gremião Isabella Dib Ferreira1,Corrêa Maria Lopes1,Caroline dos Santos Honorato Cindy1,Gonçalves Viana Paula1,Figueiredo Anna Barreto Fernandes1,Boechat Jéssica Sepúlveda1ORCID,Guerino dos Reis Érica2,Oliveira Raquel de Vasconcelos Carvalhaes3,da Silva Aline Campos de Azevedo4,Novotny Thiago Santana5,Guaraldo Lusiele6,Pereira Sandro Antonio1

Affiliation:

1. Laboratory of Clinical Research on Dermatozoonoses in Domestic Animals, Oswaldo Cruz Foundation (Fiocruz) , Rio de Janeiro , Brazil

2. Biosafety Advisory, Quality Vice-Directory, The Institute of Technology on Immunobiologicals (Bio-Manguinhos), Oswaldo Cruz Foundation (Fiocruz) , Rio de Janeiro , Brazil

3. Laboratory of Clinical Epidemiology, Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation , Rio de Janeiro , Brazil

4. Equivalence and Pharmacokinetics Service (Sefar), Oswaldo Cruz Foundation (Fiocruz) , Rio de Janeiro , Brazil

5. Medicines Sector, National Institute for Quality Control in Health (INCQS), Oswaldo Cruz Foundation (Fiocruz) , Rio de Janeiro , Brazil

6. Clinical Research Laboratory on Acute Febrile Illnesses, Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation (Fiocruz) , Rio de Janeiro , Brazil

Abstract

Abstract Itraconazole (ITZ) is the most used drug to treat feline sporotrichosis; however, little is known about its pharmacokinetics in cats with this mycosis. The aim of this study was to determine plasma ITZ concentrations in cats with sporotrichosis treated with ITZ as monotherapy or in combination with potassium iodide (KI). Cats diagnosed with sporotrichosis received orally ITZ (100 mg/cat/day) or combination therapy with ITZ (100 mg/cat/day) and KI (2.5–5 mg/kg/day) in the case of worsening or stagnation of the clinical condition. At each monthly visit, blood samples were collected at an interval of 4 h for analysis of trough and peak plasma ITZ concentrations by HPLC. Clinical features and laboratory parameters were evaluated during follow-up. Sixteen cats were included in the study. The median plasma ITZ concentration of all cats was 0.75 µg/mL. The median plasma ITZ concentration was 0.5 µg/mL in cats that received ITZ monotherapy (n = 12) and 1.0 µg/mL in those treated with ITZ + KI (n = 4). The clinical cure rate was 56.3% (n = 9) and the median treatment duration was 8 weeks. Nine cats (56.3%) developed adverse clinical reactions, and hyporexia was the most frequent (n = 8; 88.9%). Serum alanine aminotransferase was elevated in four cats (25%). The median plasma ITZ concentration detected in cats was considered to be therapeutic (>0.5 µg/mL) and was reached after 4 weeks of treatment. Plasma ITZ concentrations were higher in cats that received ITZ + KI compared to those treated only with ITZ, suggesting pharmacokinetic synergism between these drugs.

Funder

Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro

CNPq

Publisher

Oxford University Press (OUP)

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