Pharmacokinetics of voriconazole after intravenous and oral administration to healthy cats

Polina Vishkautsan, Mark G. Papich, George Richard Thompson, Jane E Sykes

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Abstract

OBJECTIVE To determine pharmacokinetics and adverse effects after voriconazole administration to cats and identify an oral dose of voriconazole for cats that maintains plasma drug concentrations within a safe and effective range. ANIMALS 6 healthy cats. PROCEDURES Voriconazole (1 mg/kg, IV) was administered to each cat (phase 1). Serial plasma voriconazole concentrations were measured for 24 hours after administration. Voriconazole suspension or tablets were administered orally at 4, 5, or 6 mg/kg (phase 2). Plasma voriconazole concentrations were measured for 24 hours after administration. Pharmacokinetics of tablet and suspension preparations was compared. Finally, an induction dose of 25 mg/cat (4.1 to 5.4 mg/kg, tablet formulation), PO, was administered followed by 12.5 mg/cat (2.05 to 2.7 mg/kg), PO, every 48 hours for 14 days (phase 3). Plasma voriconazole concentration was measured on days 2, 4, 8, and 15. RESULTS Voriconazole half-life after IV administration was approximately 12 hours. Maximal plasma concentration was reached within 60 minutes after oral administration. A dose of 4 mg/kg resulted in plasma concentrations within the target range (1 to 4 μg/mL). Adverse effects included hypersalivation and miosis. During long-term administration, plasma concentrations remained in the target range but increased, which suggested drug accumulation. CONCLUSIONS AND CLINICAL RELEVANCE Voriconazole had excellent oral bioavailability and a long half-life in cats. Oral administration of a dose of 12.5 mg/cat every 72 hours should be investigated. Miosis occurred when plasma concentrations reached the high end of the target range. Therefore, therapeutic drug monitoring should be considered to minimize adverse effects.

Original languageEnglish (US)
Pages (from-to)931-939
Number of pages9
JournalAmerican Journal of Veterinary Research
Volume77
Issue number9
DOIs
StatePublished - Sep 1 2016

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intravenous injection
Intravenous Administration
oral administration
pharmacokinetics
Oral Administration
Cats
Pharmacokinetics
cats
Tablets
Miosis
adverse effects
dosage
drugs
half life
mouth
Half-Life
Suspensions
Sialorrhea
Voriconazole
Drug Monitoring

ASJC Scopus subject areas

  • veterinary(all)

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Pharmacokinetics of voriconazole after intravenous and oral administration to healthy cats. / Vishkautsan, Polina; Papich, Mark G.; Thompson, George Richard; Sykes, Jane E.

In: American Journal of Veterinary Research, Vol. 77, No. 9, 01.09.2016, p. 931-939.

Research output: Contribution to journalArticle

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