Pharmacokinetics of voriconazole after single dose intravenous and oral administration to alpacas

Abstract

Voriconazole is a new antifungal drug that has shown effectiveness in treating serious fungal infections and has the potential for being used in large animal veterinary medicine. The objective of this study was to determine the plasma concentrations and pharmacokinetic parameters of voriconazole after single-dose intravenous (i.v.) and oral administration to alpacas. Four alpacas were treated with single 4 mg/kg i.v. and oral administrations of voriconazole. Plasma voriconazole concentrations were measured by a high-performance liquid chromatography method. The terminal half-lives following i.v. and oral administration were 8.01 +/- 2.88 and 8.75 +/- 4.31 h, respectively; observed maximum plasma concentrations were 5.93 +/- 1.13 and 1.70 +/- 2.71 microg/mL, respectively; and areas under the plasma concentration vs. time curve were 38.5 +/- 11.1 and 9.48 +/- 6.98 mg.h/L, respectively. The apparent systemic oral availability was low with a value of 22.7 +/- 9.5%. The drug plasma concentrations remained above 0.1 microg/mL for at least 24 h after single i.v. dosing. The i.v. administration of 4 mg/kg/day voriconazole may be a safe and appropriate option for antifungal treatment of alpacas. Due to the low extent of absorption in alpacas, oral voriconazole doses of 20.4 to 33.9 mg/kg/day may be needed.

A preliminary study of the plasma concentrations of orally administered fluconazole in alpacas (Vicugna pacos)

“…The animals were maintained in the field and were administered doses by the owners. Chan et al (2009) demonstrated variable bioavailability of oral voriconazole, similar to our results with fluconazole, even in a controlled environment. Different feed types may affect metabolism and consequently elimination of fluconazole (Robinson & Roeder, 2014).…”

“…Inconsistent and incomplete absorption of orally administered medications in alpacas is reported for other drugs. Median absorption of oral voriconazole, the only azole antifungal studied in alpacas and in the same structural class as fluconazole, was 20% (range 14%–39%), though it is ~96% in other animals (Chan et al, 2009). A study of 10 mg/kg of enrofloxacin delivered PO in a grain slurry to alpacas showed a mean bioavailability of nearly 30%, though the range was 12%–41% (Gandolf et al, 2005).…”

“…Consequently, doses are frequently extrapolated from true ruminant or large animal monogastric species (Fajt, 2014; Kreuder et al, 2012), which cannot always accurately predict the behavior of the drugs. Oral drug absorption in camelids can be unpredictable with a wide range of plasma concentrations in individual animals (Chan et al, 2009; Edmondson et al, 2012; Gandolf et al, 2005). The pharmacokinetics of fluconazole has not been studied in these species.…”

Coccidioidomycosis in alpacas in the southwestern United States

“…In monogastric species afflicted by coccidioidomycosis, such as dogs, cats, and horses, orally administered azole antifungal medications are the backbone of treatment, and limited literature exists regarding pharmacokinetics of various antifungal drugs in SAC. In a study of single‐dose oral voriconazole administration, the bioavailability of voriconazole was ~22% and the authors recommended doses of 20–30 mg/kg/day to achieve probable therapeutic antifungal blood levels (Chan, Duran, Walz, & Ravis, ). Similarly, other work has shown that oral medication bioavailability is lower in New World camelids compared to monogastric omnivores (Busch et al., ; Kreuder et al., ).…”

Drug Therapy in Llamas and Alpacas

“…5,6,13,14,31,32,34,37,42,[74][75][76][77][78][79][80][81][82][83][84][85] Pharmacokinetic data must be interpreted in the context of evaluating therapeutic concentrations, which depend on the type of drug and the purpose of the drug. Generalizations of the relationship between the pharmacokinetics and pharmacodynamics of antimicrobials were discussed in a previous section, and relatively good data on how to make decisions with a combination of pharmacokinetic, pharmacodynamic, and in vitro antimicrobial susceptibility data are available.…”