Pharmacokinetics anthelmintics

A review discussing anthelmintic activity, pharmacokinetics, toxicity, side effects, and clinical use of niclosamide and other anthelmintic agents is reported [95],... 

Mechanism of Action A benzimidazole carbamate anthelmintic that degrades parasite cytoplasmic microtubules, irreversibly blocks cholinesterase secretion, glucose uptake in helminth and larvae (depletes glycogen, decreases ATP production, depletes energy). Vermicidal. Therapeutic Effect Immobilizes and kills worms. Pharmacokinetics Poorly and variably absorbed from GI tract. Widely distributed, cyst fluid and including cerebrospinal fluid (CSF). Protein binding 70%. Extensively metabolized in liver. Primarily excreted in urine and bile. Not removed by hemodialysis. Half-life 8-12 hr. 

Mechanism of Action An anthelmintic agent that inhibits helminth-specific mitochondrial fumarate reductase. Therapeutic Effect Suppresses parasite production. Pharmacokinetics Rapidly and well absorbed from the gastrointestinal (Gl) tract. Rapidly metabolized in liver. Primarily excreted in urine partially eliminated in feces. Half4ife 1 2 hr... 

While broad spectrum anthelmintics (macrolide endectocides, benzimidazole carbamates, tetrahydropyrimidines) largely overlap in the range of endoparasites (mainly nematodes) they affect, the various anthelmintic classes (based on chemical structure) differ in mechanism of action, degree of activity and in pharmacokinetic properties (bioavailability, tissue distribution and... 

Some caution is, however, required when making comparisons of pharmacokinetic data. The benzimidazole anthelmintics triclabendazole and albendazole respectively show a similar spectrum of metabolites across a range of animal species including humans (21,21). However, in rats and other species, absorption of albendazole after oral administration was in excess of 30% whereas in human it was of the order of 1% (21). With triclabendazole. 

Albendazole (ABZ) is one of a class of benzimidazoles used to control helminth infections in cattle. It is generally administered as a single oral dose of 10 mg/kg b.w. either by bolus or drench. The residue levels and plasma pharmacokinetic profiles resulting from a single dose of ABZ are well documented (7). Recent studies have made important progress into alternative methods of anthelmintic... 

However, for many AMDs and indeed drugs of other classes (e.g., anthelmintics), there has long been a practice of developing slow-release (depot) formulations, administered intramuscularly, subcutaneously, or as pour-on products, for use in farm animal species. As discussed in Section 2.2.3, these products commonly display flip-flop pharmacokinetics, in which the terminal half-life represents a slow absorption phase and is longer than the elimination half-life determined after intravenous dosing. The advantages and disadvantages of depot preparations are summarized in Table 2.15. 

These pharmacokinetic interactions are established, and are likely to be clinically important when these anthelmintics are used to treat systemic worm infections. For these infections it may be necessary to increase the albendazole or mebendazole dosage in patients taking phenytoin, carbamazepine or phenobarbital. Monitor the outcome of concurrent use. The interactions are of no importance when these anthelmintics are used for intestinal worm infections (where their action is a local effect on the worms in the gut), which is the most common use of mebendazole in particular. 

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