@Garden Peas
Copy and paste from http://parasitipedia.net/index.php?option=com_content&view=article&id=2344&Itemid=2996 - Note that I did not bold any of the words, that's how they were.
Pharmacokinetics of Ivermectin
Ivermectin is a rather lipophilic molecule. Regardless of the delivery form (topical, oral or injection) it is well absorbed into blood and distributed throughout the host's organism. It tends to be deposited in the body fat and the liver, from where it is progressively released and metabolized. The pharmacokinetic behavior varies for each species and depends strongly on the delivery form and the formulation.
Absorption into blood in cattle and sheep after subcutaneous injection varies with the vehicle. After injection with a lipophilic vehicle absorption is slower than with a hydrophilic one and persistence in the organism is longer. But the blood peak reached is also lower. After oral administration (e.g. drench), absorption into blood is significantly faster, the maximum concentration achieved in blood is also higher, and it is reached earlier than after injection. The consequence is also a shorter residual effect than after injection. In cats and dogs absorption after injection is usually faster than on ruminants.
In the last years so-called long-acting (LA) injectable formulations of ivermectin (or other macrocyclic lactones) have been introduced for ruminants in many countries (e.g. Latin America). They are now very popular and have vastly replaced the slow-release boluses. Many brands contain 3,15% ivermectin, other brands slightly less or even more (up to 4%). The usual dose is 630 mcg/kg bw (instead of 200 mcg/kg bw for the classic 1% formulation). The pharmacokinetic behavior of such LA formulations is similar to the classic 1% formulation. However, the massive higher dose substantially prolongs the residual effect against most parasites, and the higher blood peaks allow higher efficacy against several parasites than the 1% formulation.
After oral administration (mainly to sheep and goats) the type and amount of feed can influence ivermectin's bioavailability. Blood concentrations achieved are lower in grazing sheep than in those fed on hay or concentrate. It is known that ivermectin and its metabolites bind strongly to food particles in the stomach. And food type can significantly influence the time that feed remains in the rumen of ruminants before passing to the abomasum. The faster the food leaves the rumen, the shorter and lower is the absorption. It has been determined that a 50% reduction of food 36 hours prior to and after drenching increases bioavailability of orally administered ivermectin in sheep by about 50%, because it prolongs the time that food remains in the rumen.
Distribution of ivermectin to all organs and most body fluids is sufficient to achieve effective concentrations against the major parasites after oral, injectable and topical administration. Highest tissue residues are detected in body fat and liver.
Excretion of ivermectin is independent from the delivery form and is achieved to >90% through bile and feces. Only about 2% is excreted through urine. About 45% of the eliminated ivermectin is the parent molecule and the rest are various metabolites. Excretion in goats is significantly faster than in sheep. In sheep it takes about 11 days for ivermectin to drop below the detectable level in blood, whereas in goats this level is reached 4 to 5 days after administration.
Withholding periods for meat vary for each host, delivery form and dosage and are between 3 and 7 weeks for the usual dose (200-300 mcg/kg bw after injection; 500 mcg/kg after pour-on administration). For the LA injectables the withholding period is usually about 4 months. Surprisingly, exactly the same formulation at the same dose and for the same target animal may have significantly different withholding periods in different countries: unfortunately regulatory authorities do not follow the same safety standards everywhere.
In lactating animals about 5% of the administered dose is excreted though the milk. It can be detected in milk already 12 hours after administration. Peak concentrations are achieved aprox. 2 days after administration. Residues in milk remain detectable during aprox. 18 days (after the usual dose of 200 mcg/kg). This is why ivermectin is usually not approved for use on dairy animals whose milk is intended for human consumption.
Injectable formulations of ivermectin are not used on horses. The reason is apparently that, shortly after introduction, it was noticed that horses were more prone to develop severe clostridial infections at the injection site (due to contamination of the needles) and other undesired side effects than cattle or sheep. In addition, the pharmacokinetic behavior of ivermectin on horses is different than in ruminants. For these reasons oral pastes were developed for horses that do not show such side effects.
Copy and paste from http://parasitipedia.net/index.php?option=com_content&view=article&id=2344&Itemid=2996 - Note that I did not bold any of the words, that's how they were.
Pharmacokinetics of Ivermectin
Ivermectin is a rather lipophilic molecule. Regardless of the delivery form (topical, oral or injection) it is well absorbed into blood and distributed throughout the host's organism. It tends to be deposited in the body fat and the liver, from where it is progressively released and metabolized. The pharmacokinetic behavior varies for each species and depends strongly on the delivery form and the formulation.
Absorption into blood in cattle and sheep after subcutaneous injection varies with the vehicle. After injection with a lipophilic vehicle absorption is slower than with a hydrophilic one and persistence in the organism is longer. But the blood peak reached is also lower. After oral administration (e.g. drench), absorption into blood is significantly faster, the maximum concentration achieved in blood is also higher, and it is reached earlier than after injection. The consequence is also a shorter residual effect than after injection. In cats and dogs absorption after injection is usually faster than on ruminants.
In the last years so-called long-acting (LA) injectable formulations of ivermectin (or other macrocyclic lactones) have been introduced for ruminants in many countries (e.g. Latin America). They are now very popular and have vastly replaced the slow-release boluses. Many brands contain 3,15% ivermectin, other brands slightly less or even more (up to 4%). The usual dose is 630 mcg/kg bw (instead of 200 mcg/kg bw for the classic 1% formulation). The pharmacokinetic behavior of such LA formulations is similar to the classic 1% formulation. However, the massive higher dose substantially prolongs the residual effect against most parasites, and the higher blood peaks allow higher efficacy against several parasites than the 1% formulation.
After oral administration (mainly to sheep and goats) the type and amount of feed can influence ivermectin's bioavailability. Blood concentrations achieved are lower in grazing sheep than in those fed on hay or concentrate. It is known that ivermectin and its metabolites bind strongly to food particles in the stomach. And food type can significantly influence the time that feed remains in the rumen of ruminants before passing to the abomasum. The faster the food leaves the rumen, the shorter and lower is the absorption. It has been determined that a 50% reduction of food 36 hours prior to and after drenching increases bioavailability of orally administered ivermectin in sheep by about 50%, because it prolongs the time that food remains in the rumen.
Distribution of ivermectin to all organs and most body fluids is sufficient to achieve effective concentrations against the major parasites after oral, injectable and topical administration. Highest tissue residues are detected in body fat and liver.
Excretion of ivermectin is independent from the delivery form and is achieved to >90% through bile and feces. Only about 2% is excreted through urine. About 45% of the eliminated ivermectin is the parent molecule and the rest are various metabolites. Excretion in goats is significantly faster than in sheep. In sheep it takes about 11 days for ivermectin to drop below the detectable level in blood, whereas in goats this level is reached 4 to 5 days after administration.
Withholding periods for meat vary for each host, delivery form and dosage and are between 3 and 7 weeks for the usual dose (200-300 mcg/kg bw after injection; 500 mcg/kg after pour-on administration). For the LA injectables the withholding period is usually about 4 months. Surprisingly, exactly the same formulation at the same dose and for the same target animal may have significantly different withholding periods in different countries: unfortunately regulatory authorities do not follow the same safety standards everywhere.
In lactating animals about 5% of the administered dose is excreted though the milk. It can be detected in milk already 12 hours after administration. Peak concentrations are achieved aprox. 2 days after administration. Residues in milk remain detectable during aprox. 18 days (after the usual dose of 200 mcg/kg). This is why ivermectin is usually not approved for use on dairy animals whose milk is intended for human consumption.
Injectable formulations of ivermectin are not used on horses. The reason is apparently that, shortly after introduction, it was noticed that horses were more prone to develop severe clostridial infections at the injection site (due to contamination of the needles) and other undesired side effects than cattle or sheep. In addition, the pharmacokinetic behavior of ivermectin on horses is different than in ruminants. For these reasons oral pastes were developed for horses that do not show such side effects.
Last edited:
