Objective—To evaluate the pharmacokinetics of a novel commercial formulation of ivermectin after administration to goats. Animals—6 healthy adult goats. Procedure—Ivermectin (200 μg/kg) was initially administered IV to each goat, and plasma samples were obtained for 36 days. After a washout period of 3 weeks, each goat received a novel commercial formulation of ivermectin (200 μg/kg) by SC injection. Plasma samples were then obtained for 42 days. Drug concentrations were quantified by use of high-performance liquid chromatography with fluorescence detection. Results—Pharmacokinetics of ivermectin after IV administration were best described by a 2-compartment open model; values for main compartmental variables included volume of distribution at a steady state (9.94 L/kg), clearance (1.54 L/kg/d), and area under the plasma concentration-time curve (AUC; 143 [ng•d]/mL). Values for the noncompartmental variables included mean residence time (7.37 days), AUC (153 [ng•d]/mL), and clearance (1.43 L/kg/d). After ...

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Algorithms for Inverse Reinforcement Learning

Avermectins and milbemycins

In recent years significant progress has been made in understanding the ecology, epidemiology and related morbidity and development of new tools for the control of soil-transmitted helminths. Such knowledge has recognized the impact of helminth infections on the health of infected groups and has created a rational basis for their control. Schoolchildren harbour some of the most intense helminthic infections, which produce adverse effects on health, growth and scholastic performance. However, although great effort has been put into targeting school-age children, women of child-bearing age and pre-school children are two other groups at high risk of morbidity due to intestinal nematode infections. Highly effective and safety-tested, single-dose anthelminthic drugs are now available, permitting periodical deworming of schoolchildren and other high-risk groups at affordable prices. Four anthelminthics against all intestinal nematodes are included in the WHO Essential Drug List (albendazole, levamisole, mebendazole and pyrantel). Recently ivermectin has also been registered for use against Strongyloides stercoralis in humans. Several well-monitored country experiences have shown that chemotherapy-based control of morbidity due to soil-transmitted helminths is possible and highly cost-effective.

Control strategies for human intestinal nematode infections

Disclosed is a rapidly disintegrating solid oral dosage form of a poorly soluble active ingredient and at least one pharmaceutically acceptable water-soluble or water dispersible excipient, wherein the poorly soluble active ingredient particles have an average diameter, prior to inclusion in the dosage form, of less than about 2000 nm. The dosage form of the invention has the advantage of combining rapid presentation and rapid dissolution of the active ingredient in the oral cavity.

Rapidly disintegrating solid oral dosage form

Described are controlled release nanoparticulate formulations comprising a nanoparticulate agent to be administered and a rate-controlling polymer which functions to prolong the release of the agent following administration. The novel compositions release the agent following administration for a time period ranging from about two to about twenty four hours or longer.

Controlled-release nanoparticulate compositions

Studies are reported which describe the effects of formulation, animal species, and route of administration on the pharmacokinetics of ivermectin. Biological half-life t1/2 increases in the order: swine (0.5 day) > dogs (1.8 day) > cattle ≌ sheep (2.8 day). Formulation modifications, based upon the solubility properties of the drug, have been directed towards the development of a nonaqueous injectable formulation for cattle and an aqueous vehicle for horses. Bioavailability following subcutaneous injection in cattle can be regulated by control of injection solvent composition: a vehicle composed of a mixed aqueous-organic solvent exhibits pharmacokinetic properties (i.e., Cp, t1/2, AUC, and F) intermediate between those furnished by an aqueous formulation and via a purely nonaqueous solvent. The longer apparent biological half-life from this latter vehicle (t1/2=8.3 days) confirms that a slow absorption process dominates the pharmacokinetics in the nonaqueous injectable product to produce an effective controlled-release formulation. These bioavailability results illustrate the increase in the concentration of an organic solvent and a concomitant decrease in surfactant concentration in a micellar aqueous system for prolonged drug delivery via injection.

https://link.springer.com/content/pdf/10.1007/BF02215150.pdf

Pharmacokinetic studies of ivermectin: effects of formulation.

lvermectin, an antiparasitic agent which is insoluble and unstable in water, is solubilized by the formation of colloidal particles, called micelles, with surface-active agents as solubilizers and stabilized by using water-miscible organic cosolvents and/or appropriate substrates in the aqueous formulation. The liquid formulations are suitable for use as parenteral or oral administration for the treatment of parasitic infections.

Solubilization of ivermectin in water

Long-acting injectable formulations are formed from a) a therapeutic agent selected from insecticides, acaricides, parasiticides, growth enhancers or oil-soluble NSAIDs, b) hydrogenated castor oil, and c) a hydrophobic carrier comprising i) triacetin, benzyl benzoate, ethyl oleate, or a combination thereof, and ii) acylated monoglycerides, propyl dicaprylates/dicaprates, caprylic/capric acid triglycerides or a combination thereof.

Long acting injectable formulations containing hydrogenated caster oil

The present invention is concerned with an oral pharmaceutical formulation containing a proton pump inhibitor (PPI) which is suitable for the treatment of gastric acid related diseases in man and animals. More specifically, the composition is a paste, and is particularly suitable for delivery of a proton pump inhibitor to horses.

Stable, ready-to-use pharmaceutical paste composition containing proton pump inhibitors

This invention relates to novel, long-acting injectable formulations. These formulations comprise: (a) a therapeutic agent selected from the group consisting of, e.g., insecticides, acaricides, parasiticides, growth enhancers and oil-soluble NASIDS; (b) hydrogenated castor oil and (c) a hydrophobic carrier comprising: (i) triacetin, benzyl benzoate or ethyl oleate or a combination thereof; and (ii) acylated monoglycerides, propyl dicaprylates/dicaprates or caprylic/capric acid triglycerides or a combination thereof. Also provided herein is a method for the treatment or prevention of various disease states by the parental administration of the invention formulations.

Williams James B

Papers

Pharmacokinetic studies of ivermectin: effects of formulation.

Solubilization of ivermectin in water

Long acting injectable formulations containing hydrogenated caster oil

Stable, ready-to-use pharmaceutical paste composition containing proton pump inhibitors

Long acting injectable formulations containing hydrogenated castor oil