Direct Determination of Avermectins in Plasma at Nanogram Levels by High-Performance Liquid Chromatography

A rational strategy for chemotherapy demands that dosage schedules be based on an adequate knowledge of clinical and biochemical pharmacology. Many anthelmintic drugs (e.g. suramin, diethylcarbamazine, hycanthone) were introduced before modern techniques for drug evaluation (controlled clinical trials) and before the development of specific and sensitive analytical methods for the assay of drugs and metabolites in biological fluids. Thus, many of the regimens used today for the treatment of parasitic diseases are largely empirically derived. By means of specific analytical methodology (high performance liquid chromatography, gas chromatography and mass-spectrometry) introduced in the 1960s, it is now possible to measure drugs and their metabolites with specificity and sensitivity. Much of this review deals with compounds which are active against the major systemic helminths, i.e., filariae (diethylcarbamazine, ivermectin and suramin) and schistosomes (niridazole, metrifonate, oxamniquine and praziquantel), but recent advances in the treatment of hydatid disease involving the benzimidazole carbamates albendazole and mebendazole are also discussed. Among the imidazole derivatives, mebendazole, a broad-spectrum anthelmintic, is poorly absorbed from the gastrointestinal tract after a therapeutic dose, but that fraction which is absorbed and escapes hepatic first-pass extraction is pharmacologically active against systemic helminths. Albendazole is more completely absorbed, but is almost undetectable in plasma due to its rapid conversion to an active sulphoxide metabolite. This compound may well become the drug of choice for the chemotherapy of echinococcosis. Levamisole, the 1-isomer of tetramisole, is rapidly and completely absorbed, but has not been widely used in systemic helminthiases because of severe side effects associated with prolonged dosage. Diethylcarbamazine is microfilaricidal against Onchocerca volvulus, but its use has been associated with major adverse effects resulting from its action on the microfilariae. These effects are related to the concentration of the drug in the plasma which, in turn, is influenced by urinary pH. The elimination half-life of diethylcarbamazine is prolonged and renal clearance reduced in alkaline urine. Under these conditions the microfilaricidal effect is enhanced, but the adverse reactions to treatment are more severe. Suramin is the only available antifilarial agent with macrofilaricidal activity. It has a long elimination half-life (36 to 54 days), and is highly (99.7%) bound to plasma protein which limits its removal from the blood.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…1987;Kojima et ai. 1987;Pivnichny et al 1983Pivnichny et al , 1987Schnitzerling & Nolan 1985;Tolan et al 1980;Tway et ai. 1981).…”

Section: Methodsunclassified

Clinical Pharmacokinetics of Anthelmintic Drugs

Edwards

Breckenridge

1988

Clinical Pharmacokinetics

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“…These are analytical methods based on high-performance liquid chromatography either by direct UV detection (Pivnichny, Shim, and Zimmerman 1983) or by fluorescence detection of ivermectin derivatives (Tolan et at. Several methods have been reported for quantifying the parent drug at low levels in biological samples.…”

Section: In Vivo Liver Metabolism Of Ivermectinmentioning

confidence: 99%

Metabolism and Tissue Residues

Chiu

1989

Ivermectin and Abamectin

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“…The fluorophor is formed by dehydration of the fused hexahydrobenzofuran ring system to a conjugated benzofuran system with a strong acid such as trifluoroacetic acid in the presence of an organic base such as methylimidazole [2,[5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Positive and negative electrospray LC–MS–MS methods for quantitation of the antiparasitic endectocide drugs, abamectin, doramectin, emamectin, eprinomectin, ivermectin, moxidectin and selamectin in milk

Durden

2007

Journal of Chromatography B

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Direct Determination of Avermectins in Plasma at Nanogram Levels by High-Performance Liquid Chromatography

Cited by 57 publications

References 11 publications

Clinical Pharmacokinetics of Anthelmintic Drugs

Clinical Pharmacokinetics of Anthelmintic Drugs

Metabolism and Tissue Residues

Positive and negative electrospray LC–MS–MS methods for quantitation of the antiparasitic endectocide drugs, abamectin, doramectin, emamectin, eprinomectin, ivermectin, moxidectin and selamectin in milk

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