Pharmacokinetics of Milbemycin Oxime in Pekingese Dogs after Single Oral and Intravenous Administration

Abstract

Objective: This study aimed to characterize the pharmacokinetic profiles of milbemycin oxime in Pekingese dogs following a single oral (PO) and intravenous (IV) dose. Six clinically healthy Pekingese dogs, with an average body weight (BW) of 4.75 kg, were included. Each dog received an IV injection of milbemycin oxime solution and PO doses of both milbemycin oxime tablets and nanoemulsion, all administered at 1 mg/kg BW.

Methods: Blood samples (∼0.6 mL) were collected at various time points, and milbemycin oxime concentrations were measured using a validated high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection. Pharmacokinetic parameters were obtained through non-compartmental analysis (NCA) using WinNonLin software.

Results: Oral administration of milbemycin oxime tablets resulted in a peak concentration (C_max) of 0.33 ± 0.07 µg/mL at 2.47 ± 1.90 h, with a mean residence time (MRT) of 21.96 ± 14.43 h and an absolute bioavailability of 51.44% ± 21.76%. In contrast, the nanoemulsion achieved a significantly higher C_max of 8.87 ± 1.88 µg/mL, with a much quicker time to peak concentration (T_max) at 0.33 ± 0.13 h, an MRT of 21.74 ± 18.21 h, and an absolute bioavailability of 99.26% ± 12.14%. After IV administration, total clearance (Cl) and steady-state volume of distribution (V_SS) were 0.13 ± 0.06 mL/kg/h and 2.36 ± 0.73 mL/kg, respectively.

Conclusions: These findings demonstrate that the milbemycin oxime nanoemulsion is absorbed more rapidly and completely, with significantly higher bioavailability than the tablet form. This suggests that the nanoemulsion could effectively overcome the issues of poor diffusion and low bioavailability associated with tablet formulations, positioning it as a promising alternative to traditional milbemycin oxime tablets.

Keywords: Pekingese dogs; bioavailability; milbemycin oxime; nanoemulsion; pharmacokinetics.

FIGURE 1

Transmission electron micrograph of milbemycin oxime nanoemulsion (×100,000 magnification).

FIGURE 2

Size distribution of milbemycin oxime nanoemulsion measured by dynamic light scattering (DLS) (one measurement).

FIGURE 3

The mean ± SD plasma concentrations of milbemycin oxime (µg/mL) in Pekingese dogs (n = 6) following a single 1 mg/kg BW dose administered as PO—tablets, PO—Nano or IV solution.