Investigation of pharmacokinetic interaction between ivermectin and praziquantel after oral administration in healthy dogs

Abstract

The purpose of this study was to determine the pharmacokinetic interaction between ivermectin (0.4 mg/kg) and praziquantel (10 mg/kg) administered either alone or co‐administered to dogs after oral treatment. Twelve healthy cross‐bred dogs (weighing 18–21 kg, aged 1–3 years) were allocated randomly into two groups of six dogs (four females, two males) each. In first group, the tablet forms of praziquantel and ivermectin were administered using a crossover design with a 15‐day washout period, respectively. Second group received tablet form of ivermectin plus praziquantel. The plasma concentrations of ivermectin and praziquantel were determined by high‐performance liquid chromatography using a fluorescence and ultraviolet detector, respectively. The pharmacokinetic parameters of ivermectin following oral alone‐administration were as follows: elimination half‐life (t1/2λz) 110 ± 11.06 hr, area under the plasma concentration–time curve (AUC0–∞) 7,805 ± 1,768 hr.ng/ml, maximum concentration (Cmax) 137 ± 48.09 ng/ml, and time to reach Cmax (Tmax) 14.0 ± 4.90 hr. The pharmacokinetic parameters of praziquantel following oral alone‐administration were as follows: t1/2λz 7.39 ± 3.86 hr, AUC0–∞ 4,301 ± 1,253 hr.ng/ml, Cmax 897 ± 245 ng/ml, and Tmax 5.33 ± 0.82 hr. The pharmacokinetics of ivermectin and praziquantel were not changed, except Tmax of praziquantel in the combined group. In conclusion, the combined formulation of ivermectin and praziquantel can be preferred in the treatment and prevention of diseases caused by susceptible parasites in dogs because no pharmacokinetic interaction was determined between them.

Development and validation of an LC–MS/MS method for the simultaneous quantification of milbemycin oxime and praziquantel in plasma: application to a pharmacokinetic study in cats

“…The LLOQ was 2.5 ng/mL for MBO and 10 ng/mL for PZQ, C-4-OH-PZQ, and T-4-OH-PZQ with a signal-to-noise (S/N) ratio > 10. The LLOQ of PZQ in this method has lower than previously reported methods ( 27 ).…”

Synergistic effects of EP‐1 and ivermectin mixture (iEP‐1) to control rodents and their ectoparasites

“…The administered dose usually 0.2-0.4 mg kg −1 has a half-life of less than 3 days in the body. [45][46][47][48][49][50] Ticks usually take a long-time to suck a large amount of blood from hosts, which means they are more easily killed by ivermectin in the blood. Fleas suck blood much less frequently, which most likely lead to insufficient amount of ivermectin intake to kill them.…”

“…Due to the toxicity to mammals, the dose of ivermectin used on human, pets and livestock is very low in order to avoid accidental poisoning. The administered dose usually 0.2–0.4 mg kg −1 has a half‐life of less than 3 days in the body 45–50 . Ticks usually take a long‐time to suck a large amount of blood from hosts, which means they are more easily killed by ivermectin in the blood.…”

The combined effect of bromadiolone and ivermectin (iBr) in controlling both rodents and their fleas

“…2015; Ozdemir et al. 2019). Heartworms and ticks are often exposed to ivermectin taken by hosts by direct contact with body fluid and by sucking a large amount of blood; thus, a low dose of ivermectin could be sufficient to kill them in a short time.…”

“…In a recent study, it was found that oral intake of ivermectin was effective in controlling ticks on rats but not very effective in removing fleas on rats (Jacob et al 2021), probably due to the very low dosage used. Pets or livestock are often treated with a low dose of ivermectin (usually 0.2-0.4 mg kg −1 ) to remove worms, ticks, or fleas (Sokol et al 2015;Ozdemir et al 2019). Heartworms and ticks are often exposed to ivermectin taken by hosts by direct contact with body fluid and by sucking a large amount of blood; thus, a low dose of ivermectin could be sufficient to kill them in a short time.…”