Comparison of the pharmacokinetics of moxidectin (Equest®) and ivermectin (Eqvalan®) in horses

Abstract

A study was undertaken in order to evaluate and compare plasma disposition kinetic parameters of moxidectin and ivermectin after oral administration of their commercially available preparations in horses. Ten clinically healthy adult horses, weighing 390-446 kg body weight (b.w.), were allocated to two experimental groups of five horses. Group I was treated with an oral gel formulation of moxidectin (MXD) at the manufacturers recommended therapeutic dose of 0.4 mg/kg bw. Group II was treated with an oral paste formulation of ivermectin (IVM) at the manufacturers recommended dose of 0.2 mg/kg b.w. Blood samples were collected by jugular puncture at different times between 0.5 h and 75 days post-treatment. After plasma extraction and derivatization, samples were analysed by HPLC with fluorescence detection. Computerized kinetic analysis was carried out. The parent molecules were detected in plasma between 30 min and either 30 (IVM) or 75 (MXD) days post-treatment. Both drugs showed similar patterns of absorption and no significant difference was found for the time corresponding to peak plasma concentrations or for absorption half-life. Peak plasma concentrations (Cmax) of 70.3+/-10.7 ng/mL (mean +/- SD) were obtained for MXD and 44.0+/-23.1 ng/mL for IVM. Moreover, the values for area under concentration-time curve (AUC) were 363.6+/-66.0 ng x d/mL for the MXD treated group, and 132.7+/-47.3 ng x d/mL for the IVM treated group. The mean plasma residence times (MRT) were 18.4+/-4.4 and 4.8+/-0.6 days for MXD and IVM treated groups, respectively. The results showed a more prolonged residence of MXD in horses as demonstrated by a four-fold longer MRT than for IVM. The longer residence and the higher concentrations found for MXD in comparison to IVM could possibly explain a more prolonged anthelmintic effect. It is concluded that in horses the commercial preparation of MXD presents a pharmacokinetic profile which differs significantly from that found for a commercial preparation of IVM. To some extent these results likely reflect differences in formulation and doses.

Comparison of the pharmacokinetics of moxidectin and ivermectin after oral administration to beagle dogs

“…The mean residence time for moxidectin was about seven-fold longer than ivermectin. Our results agree with the elimination half-life obtained in horses after oral administration of ivermectin (4.3 days) and moxidectin (23.1 days) [17]. The half-life of ivermectin in our study was similar to those obtained after subcutaneous administration of the same drug in sheep [14], cattle [16] and pigs [18].…”

“…Ivermectin is the most extensively studied of the macrocyclic agents; its disposition kinetics was studied in sheep [14,15], cattle [4,16], horses [17], pigs [18], goats [19] and camels [20]. The plasma disposition kinetics of moxidectin has been studied in sheep [21], cattle [4], horses [17], goats [22] and camels [20]. Tables 3 and 4 summarize the available fundamental Table 2.…”

Comparative pharmacokinetics of ivermectin alone and a novel formulation of ivermectin and rafoxanide in calves and sheep

“…It has been suggested that the high lipid solubility of IVM may facilitate its deposit in the adipose tissue, which may then act as a drug reservoir that contributes to the long persistence of IVM molecules in the body (Lanusse and Prichard 1993;Zulalian et al 1994). Once the drug is absorbed, it is eliminated from the circulation by metabolism, accumulation in tissues, and excretion, and the rates at which these processes contribute to termination of the action of the drug are determined by the physicochemical properties of the drug and its interaction with the specialized tissues responsible for their elimination (Perez et al 1999).…”

Pharmacokinetics and dose proportionality of oral moxidectin in beagle dogs

“…The pharmacokinetics of moxidectin has been studied in sheep [12], cattle [13], goats [14], horses [15] and camels [16]. Moxidectin is registered worldwide for the prevention of canine heartworm, but we could not locate literature reports of pharmacokinetic studies in this species.…”