Determining Pharmacokinetics of Milbemycin Oxime in Pekingese Dogs with HPLC

Researchers at Henan University of Science and Technology (Luoyang, China) attempted the characterization of pharmacokinetic profiles of milbemycin oxime in Pekingese dogs following a single oral (PO) and intravenous (IV) dose. Blood samples from six clinically healthy dogs receiving an IV injection of milbemycin oxime solution and PO doses of both milbemycin oxime tablets and nanoemulsion were collected at various time points, with milbemycin oxime concentrations measured using a validated high performance liquid chromatography (HPLC) method with ultraviolet (UV) detection. A paper based on this study was published in Veterinary Medicine and Science (1).

A novel semi-synthetic macrolide anthelmintic, composed of 80% A4 derivatives and 20% A3 derivatives of 5-didehydromilbemycin (2), milbemycin oxime is specifically designed to control both internal and external parasites in dogs and cats, effectively targeting internal parasites, such as hookworms, roundworms, and whipworms, as well as external parasites like heartworms, mange, lice, and fleas (3–5).Pharmacokinetic research on milbemycin oxime in dogs is limited, with most studies focusing on beagles (6–8), which typically have an average body weight of approximately 10 kg (9). In contrast, Pekingese dogs, a popular breed in China known for their petite size, charming appearance, and gentle demeanor, have not been studied in this context (9).

The method used in extracting the milbemycin oxime from plasma samples, and the chromatographic analysis which followed, was adapted from a previous report with minor modifications (8). All extracts were evaporated at 45 °C under a stream of nitrogen. The residue was then dissolved in 300 µL of the mobile phase, vortexed for 90 s, and filtered through a 0.22 µm microporous filter membrane into an autosampler glass vial. A 20 µL aliquot of the supernatant was injected into an HPLC system for analysis. The mobile phase consisted of 14% 0.5 mmol/L ammonium acetate buffer and 86% acetonitrile, with a flow rate of 1 mL/min. The detection wavelength was set at 249 nm, and the column temperature was maintained at 25 °C (1).

The authors of the study report that their analysis demonstrates that milbemycin oxime nanoemulsion has a favorable pharmacokinetic profile, including rapid absorption, wide distribution, and slow elimination in Pekingese dogs. Its absolute bioavailability was 99.26% ± 12.14%, significantly higher than that of milbemycin oxime tablets, thus suggesting that milbemycin oxime nanoemulsion could successfully replace milbemycin oxime tablets as a new dosage form for the treatment of canine parasitosis. However, they conclude that further pharmacodynamic studies are needed to validate this recommendation due to the significant differences in pharmacologic and pharmacokinetic parameters of milbemycin oxime in various breeds of dogs (1).

Pekingese. © deviddo - stock.adobe.com

References

1. Li, Z. E.; Duan, M. H.; Dai, Y.; et al. Pharmacokinetics of Milbemycin Oxime in Pekingese Dogs after Single Oral and Intravenous Administration. Vet. Med. Sci. 2025, 11 (2), e70312. DOI: 10.1002/vms3.70312

2. Tsukamoto, Y.; Sato, K.; Mio, S.; et al. Synthesis of 5-keto-5-oxime Derivatives of Milbemycins and Their Activities Against Microfilariae. Agric.Biol. Chem. 1991, 55 (10), 2615–2621. DOI: 10.1271/bbb1961.55.2615

3. Hayes, B.; Wiseman, S.; Snyder, D. E. Field Study to Investigate the Effectiveness and Safety of a Novel Orally Administered Combination Drug Product Containing Milbemycin Oxime and Lotilaner (Credelio® Plus) Against Natural Intestinal Nematode Infections in Dogs Presented as Veterinary Patients in Europe. Parasites Vectors 2021,14 (1), 258. DOI: 10.1186/s13071-021-04808-0

4. Lee, H. H.; Terada, M. In vitro Effects of Milbemycin Oxime: Mechanism of Action Against Angiostrongylus cantonensis and Dirofilaria immitis. Parasitol. Res. 1992, 78, 349–353. DOI: 10.1007/BF00937095

5. Young, L. M.; Wiseman, S.; Crawley, E.; et al. Effectiveness of Credelio® Plus, a Novel Chewable Tablet Containing Milbemycin Oxime and Lotilaner for the Treatment of Larval and Immature Adult Stages of Toxocara canis in Experimentally Infected Dogs. Parasites Vectors 2021, 14 (1), 256. DOI: 10.1186/s13071-021-04762-x

6. Holmstrom, S. D.; Totten, M. L.; Newhall, K. B.; Qiao, M.; Riggs, K. L. Pharmacokinetics of Spinosad and Milbemycin Oxime Administered in Combination and Separately per OS to Dogs. J. Vet. Pharmacol. Ther. 2012, 35 (4), 351–364. DOI: 10.1111/j.1365-2885.2011.01333.x

7. Letendre, L.; Harriman, J.; Drag, M.; Mullins, A.; Malinski, T.; Rehbein, S. The Intravenous and Oral Pharmacokinetics of Afoxolaner and Milbemycin Oxime When Used as a Combination Chewable Parasiticide for Dogs. J. Vet. Pharmacol. Ther. 2017, 40 (1), 35–43. DOI: 10.1111/jvp.12332

8. Lu YiTong, L. Y.; Qi LianWen, Q. L.; Xu QianQian, X. Q.; et al. Pharmacokinetics of Milbemycin Oxime in Dogs Following Its Intravenous and Oral Administration. J. Northeast Agric. Univ. (English Edition) 2018, 25(1), 47–54. https://www.cabidigitallibrary.org/doi/full/10.5555/20183140743

9. Yang, F.; Yang, F.; Wang, H.; et al. Pharmacokinetics of Ceftiofur Sodium in Peekapoo Dogs Following a Single Intravenous and Subcutaneous Injection. J. Vet. Pharmacol. Ther. 2020, 43 (4), 325–330. DOI: 10.1111/jvp.12866