Abstract
Loxodonta africana are susceptible to a wide variety of parasites that are often treated with the broad-spectrum antiparasitic ivermectin.1,6 The purpose of this study with African elephants was to (1) measure plasma ivermectin levels following administration of 0.1 mg/kg ivermectin PO, (2) compare plasma ivermectin levels following administration with regular versus restricted feed rations, and (3) measure ivermectin excretion in feces. Using a crossover design, six elephants were divided into two groups. Typical food rations were provided with ivermectin (ProMectin E, Vedco, Inc., St. Joseph, MO, USA) administration in the first group, and rations were withheld for 2 hours following administration in the second group. Blood and fecal samples were collected for 7 days following drug administration. After a 5-week washout period, groups were switched, and the procedure was repeated. Plasma ivermectin was analyzed using HPLC (high-performance liquid chromatography). Combined results are presented in the table below, since there was no detectable difference in the pharmacokinetic data between the “fed” and “fasted” groups. Tmax demonstrated rapid absorption and was similar to parameters reported for horses.5 Cmax and MRT are substantially lower than values reported following 0.2 mg/kg PO dosing in horses5 and cattle.3 High ivermectin concentrations were excreted in feces, indicating substantial adsorption of ivermectin to particulate material in the digesta. This phenomenon is a significant factor modulating the oral ivermectin absorption process in ruminants.4 Although ivermectin may be effective for treating some infections in elephants at a dosage of 0.1 mg/kg, the resulting low plasma concentrations may affect the antiparasitic efficacy, particularly against ectoparasites. A dosage of 0.2–0.4 mg/kg PO would probably be more effective at eliminating dose-limiting parasites and may minimize development of parasite resistance. Further investigation into routes of administration such as topical would be beneficial.
Table 1. The pharmacokinetics of ivermectin following oral administration to African elephants
|
|
Plasma
|
Feces
|
|
Cmax (ng/ml)a
|
7.2
|
1274.0
|
|
Tmax (days)b
|
0.33
|
|
|
AUC (ng*d/ml)c
|
18.75
|
1680.5
|
|
MRT (days)d
|
3.0
|
|
|
T½ (days)e
|
3.65
|
1.0
|
aMaximum plasma concentration
bTime to maximum plasma concentration
cArea under the curve
dMean residence time
eElimination half-life
Acknowledgments
The authors would like to thank the Pittsburgh Zoo and PPG Aquarium Conservation Fund for support of this study.
Literature Cited
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