Plasma concentrations of fenbendazole (FBZ) and oxfendazole in alpacas (Lama pacos) after single intravenous and oral dosing of FBZ

Figures & data

Figure 1 Plasma concentrations of FBZ and OFZ in alpacas after iv administration of FBZ in a DMSO/propylene glycol vehicle.

Notes: Mean ± SEM values for the plasma concentrations of FBZ (—•—) and OFZ (—▪—) after iv administration of FBZ in DMSO/propylene glycol (50 mg/mL) to five alpacas. Inset: Plasma concentration versus time curve of OFZ after iv administration of FBZ on an enlarged scale to demonstrate the appearance of OFZ.
Abbreviations: DMSO, dimethyl sulfoxide; FBZ, fenbendazole; iv, intravenous; OFZ, oxfendazole; SEM, standard error of the mean.

Figure 2 Plasma concentrations of FBZ and OFZ in alpacas after oral administration of FBZ suspension.

Notes: Mean ± SEM values for the plasma concentrations of FBZ (—•—) and OFZ (—▪—) after oral administration (5 mg/kg) of FBZ.
Abbreviations: FBZ, fenbendazole; OFZ, oxfendazole; SEM, standard error of the mean.

Table 1 Pharmacokinetic analysis of fenbendazole after iv dosing in a DMSO/propylene glycol vehicle

Parameters	Units	Mean ± SEM	Range
A	µg/mL	9.8±1	7–13.7
α	h^−1	16±5	2.3–32.2
B	µg/mL	1.4±0.3	0.42–2.3
β	h^−1	0.4±0.15	0.03–0.9
Cpmax	µg/mL	11.3±1	8.2–15.5
k10	h^−1	2.5±0.9	0.5–4.8
k12	h^−1	11.8±3.9	1.5–24
k21	h^−1	2.5±0.7	0.2–4.8
CL	mL/min/kg	16.5±4.4	4–31
Vss	mL/kg	3,345±1,042	1,713–7,433
$T_{1/2k_{10}}$	hour	0.6 ± 0.2	0.15–1.0
T1/2α	hour	0.1±0.05	0.02–0.3
T1/2β	hour	5.9±3.8	0.8–21
AUC	h µg/mL	7.7±2.5	2.7–20
AUMC	h^Citation2 µg/mL	92±72	2–376
MRT	hour	7±4	2–19

Notes: Plasma concentration versus time data best fit a two-compartment model. The two-compartment open model for the pharmacokinetic analysis of plasma fenbendazole concentration versus time data after iv administration of 5 mg/kg fenbendazole in DMSO:propylene glycol to five alpacas is shown. Raw concentration versus time data were weighted 1/y² before analysis. A and B are the zero-time intercepts of the concentration axis and represent the extrapolated plasma concentrations for the distribution and elimination phases, respectively. The macro rate constants are α (distribution), β (elimination), and half-lives (T_1/2α and T_1/2β) of distribution and elimination, respectively. C_pmax is the maximum concentration (A + B). k₁₀ is the rate at which the drug leaves the body from the central compartment. The first-order rate constants k₁₂ and k₂₁ denote the rate of change from the central compartment to the peripheral compartment (k₁₂) and from the peripheral compartment back to the central compartment (k₂₁); CL is total clearance; V_ss is the volume of distribution at steady state. Also listed are the area under the curve (AUC), area under the moment curve (AUMC), and mean residence time (MRT).

Abbreviations: DMSO, dimethyl sulfoxide; iv, intravenous; SEM, standard error of the mean.

Table 2 Statistical moment analysis of FBZ and OFZ in alpacas after oral administration of FBZ suspension (5 mg/kg)

Parameter	Mean ± SEM (range)
	FBZ	OFZ
AUC (h µg/mL)	6±2.6 (0.7–14)	8±3 (0.7–19)
Percentage of total AUC	47±7 (32–65)	53±7 (35–68)
$T_{1/2{\lambda }_z}\text{(hours)}$	23±5 (9–37)	NA
MRT (hours)	39±7 (17–54)	40±4.8 (31–58)
Cmax (µg/mL)	0.12±0.05 (0.05–0.28)	0.14±0.05 (0.05–0.31)
Tmax (hours)	9.6±1 (8–12)	24±6.6 (12–48)
F (%)	15±6 (1–41)	NA

Notes: Noncompartmental statistical moment analysis of FBZ and OFZ in the sera of five alpacas after oral administration of fenbendazole (5 mg/kg). T_1/2λz is the terminal-phase half-life; T_max is the time to achieve C_max; C_max is the maximum plasma concentration. AUC was calculated from the concentration versus time curve using the trapezoidal rule and extrapolated to infinity. For FBZ, the AUC was extrapolated to infinity using the last-measured concentration divided by λ_z (the slope of the terminal phase of the curve using at least three time points). For OFZ, AUC was calculated to the last-measured plasma concentration. Mean residence time (MRT, in hours) was calculated using AUMC/AUC. F% represents the fractional absorption of FBZ after oral administration.

Abbreviations: AUC, area under the concentration versus time curve; FBZ, fenbendazole; NA, not applicable; OFZ, oxfendazole; SEM, standard error of the mean; AUMC, area under the moment curve.

NavarreCBRavisWRNagillaRSimpkinsADuranSHPughDGPharmacokinetics of phenylbutazone in llamas following single intravenous and oral dosesJ Vet Pharmacol Ther20012422723111442803

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