The antiparasitic moxidectin: Safety, tolerability, and pharmacokinetics in humans

Journal of Clinical Pharmacology

Volumn 43, Issue 10, 2003, Pages 1108-1115

  Cotreau, Monette M ^a   Warren, Sarah ^a   Ryan, John L ^a   Fleckenstein, Lawrence ^c   Vanapalli, Sreenivasa R ^c   Brown, Kenneth R ^d   Rock, David ^b   Chen, Chieh Yu ^a   Schwertschlag, Ullrich S ^a  

^a PFIZER INC   (United States)

^b ZOETIS   (United States)

^c UNIVERSITY OF IOWA   (United States)

^d UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Moxidectin; Onchocerciasis; Parasites; Pharmacokinetics

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR; ALKALINE PHOSPHATASE; ANTIPARASITIC AGENT; CHLORIDE; CREATININE; CYTOCHROME P450 3A; EQUEST; GAMMA GLUTAMYLTRANSFERASE; MACROLIDE; MILBEMYCIN DERIVATIVE; MOXIDECTIN; PHOSPHORUS; PLACEBO; PROHEART; QUEST; SODIUM; VETERINARY DRUG;

ADULT; ALKALINE PHOSPHATASE BLOOD LEVEL; AREA UNDER THE CURVE; ARTICLE; BLOOD TOXICITY; CENTRAL NERVOUS SYSTEM DISEASE; CHLORIDE BLOOD LEVEL; CLINICAL TRIAL; COHORT ANALYSIS; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CREATININE BLOOD LEVEL; DIET RESTRICTION; DISEASE SEVERITY; DISTRIBUTION VOLUME; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG ELIMINATION; DRUG HALF LIFE; DRUG SAFETY; DRUG SCREENING; DRUG TOLERABILITY; EOSINOPHILIA; GAMMA GLUTAMYL TRANSFERASE BLOOD LEVEL; HEADACHE; HUMAN; HUMAN EXPERIMENT; INFECTION; LABORATORY TEST; LETHARGY; LEUKOCYTOSIS; LEUKOPENIA; LIPID DIET; MALE; MONOCYTOSIS; NAUSEA AND VOMITING; NORMAL HUMAN; ONCHOCERCIASIS; PHARMACOKINETICS; PHARYNGITIS; PHOSPHATE BLOOD LEVEL; PHYSICAL EXAMINATION; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE; SODIUM BLOOD LEVEL; SOMNOLENCE; TOOTH INFECTION; UPPER RESPIRATORY TRACT INFECTION; VERTIGO; VIRUS INFECTION;

ADMINISTRATION, ORAL; ADOLESCENT; ADULT; ANTIPARASITIC AGENTS; COHORT STUDIES; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; EATING; FASTING; FOOD-DRUG INTERACTIONS; HUMANS; MACROLIDES; MALE; MIDDLE AGED; NAUSEA; ONCHOCERCIASIS; TREATMENT OUTCOME; VOMITING;

EID: 0141653850     PISSN: 00912700     EISSN: None     Source Type: Journal    
DOI: 10.1177/0091270003257456     Document Type: Article

References (39)

1. Basanez MG, Boussinesq M: Population biology of human onchocerciasis. Phil Trans R Soc Lond B 1999;354:809-826.
2. Plaisier AP, van Oortmarssen GJ, Remme J, Habbema JD: The reproductive lifespan of Onchocerca volvulus in West Africa savanna. Acta Trop 1991;48:271-284.
3. Hall LR, Pearlman E: Pathogenesis of onchocercal keratits (river blindness). Clin Microbiol Rev 1999;12:445-453.
4. Ottesen EA: Immune responsiveness and the pathogenesis of human onchocerciasis. J Inf Dis 1995;171:659-671.
5. Tagboto SK, Townson S: Onchocerca volvulus and O. lienalis: the microfilaricidal activity of moxidectin compared with that of ivermectin in vitro and in vivo. Ann Trop Med Parasitol 1996;90:497-505.
6. Rathinam SR, Cunningham ET: Infectious causes of uveitis in the developing world. Int Ophthalmol Clin 2000;40:137-152.
7. World Health Organization: Onchocerciasis and its control. WHO Tech Rep Ser 1995;852:1-103.
8. Forrester SG, Prichard RK, Beech RN: A glutamate-gated chloride channel subunit from Haemonchus contortus: expression in a mammalian cell line, ligand binding, and modulation of anthelmintic binding by glutamate. Biochem Pharmacol 2002;63:1061-1068.
9. Cully DF, Vassilatis DK, Liu KK, Paress PS, Van der Ploeg LHT, Schaeffer JM, et al: Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans. Nature 1994;371:707-711.
10. Arena JP, Liu KK, Paress PS, Schaeffer JM, Cully DF: Expression of a glutamate-activated chloride current in Xenopus oocytes injected with Caenorhabditis elegans RNA: evidence for the modulation by avermectin. Mol Brain Res 1992;15:339-348.
11. Cully DF, Wilkinson H, Vassilatis DK, Etter A, Arena JP: Molecular biology and electrophysiology of glutamate-gated chloride channels of invertebrates. Parasitology 1996;113:S191-S200.
12. Martin RJ: An electrophysiological preparation of Ascaris suum pharyngeal muscle reveals a glutamate-gated chloride channel sensitive to the avermectin analogue, milbemycin D. Parasitology 1996;112:247-252.
13. Blackhall WJ, Pouliot JF, Prichard RK, Beech RN: Haemonchus contortus: selection at a glutamate-gated chloride channel gene in ivermectin- and moxidectin-selected strains. Exp Parasitol 1998;90:42-48.
14. Zulalian J, Stout SJ, daCunha AR, Garces T, Miller P: Absorption, tissue distribution, metabolism, and excretion of moxidectin in cattle. J Agric Food Chem 1994;42:381-387.
15. Perez R, Cabezas I, Garcia M, Rubilar L, Sutra JF, Galtier P, et al: Comparison of the pharmacokinetics of moxidectin (Equest®) and ivermectin (Equalan®) in horses. J Vet Pharmacol Therap 1999;22:174-180.
16. Alvinerie M, Escudero E, Sutra JF, Eeckhoutte C, Galtier P: The pharmacokinetics of moxidectin after oral and subcutaneous administration to sheep. Vet Res 1998;29:113-118.
17. Vanapalli SR, Hung YP, Fleckenstein L, Dzimianski MT, McCall JW: Pharmacokinetics and dose proportionality of oral moxidectin in beagle dogs. Biopharm Drug Dispos 2002;23:263-272.
18. Craven J, Bjorn H, Hennessy D, Friis C, Nansen P: Pharmacokinetics of moxidectin and ivermectin following intravenous injection in pigs with different body compositions. J Vet Pharmacol Therap 2001;24:99-104.
19. 14C-moxidectin by hepatic microsomes from various species. Vet Res Comm 2001;25:345-354.
20. 14C moxidectin in cultured rat hepatocytes. J Vet Pharmacol Therap 2001;24:171-177.
21. 14C-labeled moxidectin in horses. J Agric Food Chem 1997;45:3627-3633.
22. 14C-labeled moxidectin in sheep. J Agric Food Chem 1994;42:1767-1773.
23. Chen Y-C, Hung Y-P, Fleckenstein L: Liquid chromatographic assay of moxidectin in human plasma for application to pharmacokinetic studies. J Pharm Biomed Anal 2002;29:917-926.
24. World Health Organization: A suitable macrofilaricide. TDR News 2000;62:11.
25. Brown KB: The use of macrocyclic lactones to control parasites of humans, in: Vercruysse J, Rew RS (eds.), Macrocyclic Lactones in Antiparasitic Therapy. New York: CABI, 2002;405-413.
26. Taylor HR, Trpis M, Cupp EW, Brotman B, Newland HS, Soboslay PT, et al: Ivermectin prophylaxis against experimental Onchocerca volvulus infection in chimpanzees. Am J Trop Med Hyg 1988;39:86-90.
27. Chavasse DC, Post RJ, Davies JB, Whitworth JA: Absence of sperm from the seminal receptacle of female Onchocerca volvulus following multiple doses of ivermectin. Trop Med Parasitol 1993;44:155-158.
28. Duke BO, Zea-Flores G, Castro J, Cupp E, Munoz B: Effects of multiple monthly doses of ivermectin on adult Onchocerca volvulus. Am J Trop Med Hyg 1990;43:657-664.
29. Guzzo CA, Furtek CI, Porras AG, Chen C, Tipping R, Clineschmidt CM, et al: Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in healthy adult subjects. J Clin Pharmacol 2002;42:1122-1133.
30. Steel JW: Pharmacokinetics and metabolism of avermectins in livestock. Vet Parasitol 1993;48:45-57.
31. Schinkel AH, Smitt JJ, Van Tellingen O, Beijnen JH, Wagenaar E, Van Deemter L, et al: Disruption of the mouse mdr 1a p-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 1994;77:491-502.
32. Pouliot J-F, L'Heureux F, Liu Z, Prichard RK, Georges E: Reversal of P-glycoprotein-associated multidrug resistance by ivermectin. Biochem Pharmacol 1997;53:17-25.
33. Blackhall WJ, Liu HY, Xu M, Prichard RK, Beech RN: Selection at a P-glycoprotein gene in ivermectin- and moxidectin-selected strains of Haemonchus contortus. Mol Biochem Parasitol 1998;95:193-201.
34. Molento MB, Prichard RK: Effects of the multidrug-resistance-reversing agents verapamil and CL 347, 099 on the efficacy of ivermectin or moxidectin against unselected and drug-selected strains of Haemonchus contortus in jirds (Meriones unguiculatus). Parasitol Res 1999;85:1007-1011.
35. Mealy KL, Bentjen SA, Waiting DK: Frequency of the mutant MDR1 allele associated with ivermectin sensitivity in a sample population of collies from the northwestern United States. Am J Vet Res 2002;63:479-481.
36. Mealey KL, Bentjen SA, Gay JM, Cantor GH: Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr 1 gene. Pharmacogenetics 2001;11:727-733.
37. Paul AJ, Tranquilli WJ, Hutchens DE: Safety of moxidectin in avermectin-sensitive collies. Am J Vet Res 2000;61:482-481.
38. Beal MW, Poppenga RH, Birdsall WJ, Hughes D: Respiratory failure attributable to moxidectin intoxication in a dog. J Am Vet Med Assoc 1999;12:1813-1817.
39. Schaeffeler E, Eichelbaum M, Brinkmann U, Penger A, Asante-Poku S, Zanger UM, et al: Frequency of C3435T polymorphism of MDR1 gene in African people. Lancet 2001;358:383-384.