Pharmacokinetics of ivermectin in sheep following intravenous, intra‐abomasal or intraruminal administration*

Abstract

The pharmacokinetics of ivermectin in plasma following intravenous, intra-abomasal, and intraruminal administration to sheep was determined. When given intravenously, ivermectin was very slowly eliminated with a terminal half-life of 178 h and a volume of distribution at steady state of 5.3 l/kg indicating sequestration in a temporary depot. Intra-abomasal administration resulted in rapid absorption, a peak plasma concentration of 60.6 ng/ml at 4.4 h, and 100% bioavailability. However, intraruminal administration produced a much lower peak concentration (17.6 ng/ml at 23.5 h) and bioavailability (25.1%). A subsequent in vitro study indicated that ivermectin may be rapidly metabolized in the rumen.

A pharmacokinetic model to document the actual disposition of topical ivermectin in cattle

“…Selection of a model with two separate gastrointestinal compartments suggests that the local disposition of ivermectin is not the same at all sites of the gastrointestinal tract in terms of (re-)absorption and elimination. This is in line with the experimental finding of a different bioavailability of ivermectin in the rumen and in the abomasum in sheep (75% lower after intraruminal administration than after intra-abomasal administration) [21]. This difference in bioavailability was first attributed to an extensive degradation or metabolisation of ivermectin in the rumen [21].…”

“…This is in line with the experimental finding of a different bioavailability of ivermectin in the rumen and in the abomasum in sheep (75% lower after intraruminal administration than after intra-abomasal administration) [21]. This difference in bioavailability was first attributed to an extensive degradation or metabolisation of ivermectin in the rumen [21]. This explanation, however, is difficult to conciliate with our results, since the unabsorbed fraction of ingested ivermectin was fully recovered in the faeces of the lickers.…”

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

“…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].…”

Synopsis

“…Both the therapeutic and persistent efficacy of ivermectin injection against O. ovis were higher than those of oral ivermectin (Dorchies et al, 1997). The greater efficacy of sc injected endectocides is related to pharmacokinetics; the bioavailability of ruminally administered ivermectin was only 25%, whereas that of subcutaneously injected ivermectin was 100% (Prichard et al, 1985). The initial explanation to the low utilisation of orally administered drug was that it was probably metabolised in the rumen, but later evidence indicates that ivermectin is bound to the particles of the digesta (Andrew & Halley, 1996).…”