Half-life anthelmintics

Anthelmintic, antiprotozoal, anti-neoplastic, and antiviral agent Binds many proteins, i.e., cytokines. epidermal growth factor, and members of the FGF family inhibits dengue virus infec-tivity of host cells very long in vivo half-life, exhibits a wide range of toxic side effects 40-47... 

Diethylcarbamazine is an anthelmintic drug that does not resemble other antiparasitic compounds although it has some relationship with piperazine derivatives and it has been useful in the management of filariasis due to Wuchereria bancrofti or Brugia malayi and Loa loa and of tropical eosinophilia. It is a lipoxygenase inhibitor and alters the surface structure of the parasite making it more susceptible to destruction by the host. It is well absorbed and widely distributed. It is eliminated with an half-life of 5-13 hours both by metabolism and excretion unchanged in the urine. 

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. 

Macrocyclic lactones are highly lipophilic and are distributed widely to and eliminated slowly from the body compartments such that they have persistent anthelmintic activity. There are physicochemical differences between ivermectin and moxidectin that confers different lipid solubility on each drug moxidectin has a much longer half-life in body fat (Afzal et al 1997). This constitutes at least a partial explanation for the longer period of suppression of equine fecal worm egg output achieved following dosing with moxidectin compared with ivermectin (Jacob et al 1995,... 

Although thiabendazole shows broad-spectrum activity against different helminths in humans and animals, it suffers from the limitation of being readily metabolised to form the inactive 5-hydroxythiabendazole (3, R=OH), with a half-life of only n minutes in rats [7]. To prevent this enzymatic hydroxylation of the drug at 5-position, Merck scientists synthesized a variety of 5-substituted thiabendazoles, of which 5-aminothiabendazole (4) and 2-(thiazol-4-yl)-5-isopropylcarbonylami-nobenzimidazole (5, cambendazole) showed promising activity. The better anthelmintic activity of 4 and 5 compared to thiabendazole has been attributed to their longer half-life [8,9]. 

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. 

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