A Abametapir‐Based Formulation 130 Absorption, Distribution

353 Index a amitraz 97, 98, 100, 101, 152, 171, 172, 176, abametapir‐based formulation 130 178, 179, 232, 308 absorption, distribution, metabolism and Anaplasma phagocytophilum 44, 276, 309 excretion (ADME) 263, 274, 280–282 ancestral ticks 25, 32 acaricide classes 96, 98, 101, 110, 116 animal ectoparasiticide products 8 acaricide resistance 101, 102, 110–112, animal vector‐transmitted pathogens 64–74 115, 116 anthelmintic resistance 7, 13, 14 acetylcholine (AChE) 97 antiparasitic drugs 12, 15–16, 151, 245, acetylcholinesterase 100, 114, 121 254, 260 active pharmaceutical ingredient (API) 13, anti‐tick vaccines 143, 144, 156, 157, 16, 274, 321 195, 211 adult immersion test (AIT) 111–112 aquaporins 30, 145 afoxolaner arsenicals 97 – chemical‐biological structure‐activity Argasidae 25, 60, 61, 81, 86, 141, 144 relationships 261–266 arthropod ectoparasites 245–246 – distribution and clearance in artificial feeding systems (AFSs) dogs 282–284 – blood meal 189–190 – dose level selection 277–279 – components 188–191 – flea control 259 – ectoparasiticide drug discovery 197–198 – formulation selection 279–280 – fleas 191 – mode of action 266–270 – flies 196 – naphthalene chemistry 260 – hematophagous hemiptera 196–197 ® – NexGard 235 – insect laboratory cultures 188 – oral pharmacokinetics in dogs 280–282 – lice 196 – plasma concentration 198, 277–279, – membranes 188–189 281–283, 291 – methods and applications 191–196 – proof of concept in dogs 277 – mites 196–197 – protein binding 283 – mosquitoes 195–196 – safety in dogs 284–285 – temperature control systems 190–191 – safety pharmacology profile 284 – ticks 191–195 – study compliance with regulatory ATP‐binding cassette (ABC) requirements 275–276 transporter 126, 152 – topical and oral treatment 259 agricultural pests 7, 18, 183 b agrochemical pesticide development 15 Babesia spp. 276 Amblyomma hebraeum voraxin 145 babesiosis 6 Amblyomma maculatum 297 Bayer Animal Health 10, 16 Ectoparasites: Drug Discovery Against Moving Targets, First Edition. Edited by Charles Q. Meng and Ann E. Sluder © 2018 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2018 by Wiley-VCH Verlag GmbH & Co. KGaA. bindex.indd 353 5/3/2018 2:48:08 PM 354 Index bedbugs 216–217 concealed antigens 26, 28, 35, 144, 156 benzyl alcohol‐containing formulations 128 Ctenocephalides felis 189, 215, 231, 245, bioassays 251, 263, 276, 296, 333 – adult immersion test 111 current Good Manufacturing Process – ectoparasiticide discovery 111 (cGMP) 275 – larval immersion test (LIT) 112–113 cysteine‐loop ligand‐gated chloride channels – larval packet test (LPT) 112 (CysLGCCs) 247 – larval tarsal test (LTT) 113–114 cytochrome P450 monooxygenases 123, biochemical tools 114 126 Biopharmaceutics Classification System (BCS) 281 d blood coagulation processes 32 demodicosis 288, 289, 307 blood‐feeding ectoparasites 43 Dermacentor variabilis 6, 30, 63, 85, 154, body louse prevalence 6 177–179, 213, 269, 277, 297 Boophilus yolk pro‐cathepsin D (BYC) 154 – vs. afoxolaner plasma concentration 279 Borrelia burgdorferi 5, 6, 25, 44, 58, 66, 86, dieldrin 97, 100, 246–247, 254, 270, 298 276, 289, 290, 306, 309, 310, 312 dieldrin‐resistant 198, 249 Borrelia duttoni 61, 86 diethylmaleate (DEM) 99 bradykinin 35, 36 dimethicone‐based formulations 128–129 ® Bravecto 16, 235, 248, 255, 256, 5,5ʹ‐dimethyl‐2,2ʹ‐bipyridyl 130 310–312, 321 dimeticone‐based anti‐louse product 129 Dipylidium caninum 4, 44, 74, 276 c divalent metal‐transporter 1 (DMT1) 151, carbamates 8, 97, 121, 175, 176, 179, 184, 155 232 dog adult flea model 230 carbaryl 97, 121, 184 doramectin 98, 237 carboxylesterases 114, 126, 131 dose confirmation carrier proteins (CPs) 151, 153 – additional efficacy studies 288–290 cat fleas 52, 174, 189, 191, 207, 215, 216, – field trials 287–288 231, 232, 260, 261, 263, 269, 276, 296, – fleas 285–287 322, 333 – ticks 287 cathepsin B (CatB) 148–150 drug sensitivity status, of tick populations cathepsin C (CatC) 147–149 – acaricide resistance 110–111 cathepsin D (CatD) 147, 148, 154 – adult immersion test (AIT) 111–112 cathepsin L (CatL) 148, 151 – biochemical tools 114 cattle ticks – larval immersion test (LIT) 112–113 – arsenicals 97 – larval packet test (LPT) 112 – carbamates 97 – larval tarsal test (LTT) 113–114 – formamidines 97–98 – molecular tools 114–115 – growth regulators 98–99 – resistance bioassays 115–116 – Rhipicephalus (Boophilus) microplus 95 – resistance management 116 – macrocyclic lactones 98 Drugs for Neglected Diseases Initiative – natural products 99 (DNDi) 16 – organochlorine 97 – organophosphates (OP) 97 e – phenylpyrazoles 98 ectoparasite and endoparasite control – resistance management 100–103 – adult flea infestation 5 – resistance mechanisms of 99–100 – advantage 167–168 – synthetic pyrethroids 98 – approaches for 4–7 central nervous system (CNS) 247, 284 – assay implementation 171–172 chloride channels 249–252, 254, 256 – body louse prevalence 6 chlorpyrifos 173, 175 – canine and feline heartworm prevention 7 Companion Animal Parasite Council – ectoparasite challenges 10–12 (CAPC) 5 – ectoparasiticides 7–9 bindex.indd 354 5/3/2018 2:48:08 PM Index 355 – endoparasite challenges 12–14 – – flow charts 224 – endoparasiticides 9–10 – – host animal models 230 – energy balance 5 – – laboratory animal models 229 – flow charts 168 – – pre‐clinical development studies 226 – fly repellents 5 – – product characteristics 237–229 – heartworm larvae 7 – – role of animal models 223–227 – host physiology 167 ectoparasiticide products – limitations 167–168 – companion animals – livestock 237 – – control collars for 232–233 – macrocyclic lactone (ML)‐based – – macrocyclic lactone (ML) 236 anthelmintic 7 – – oral administration 233–236 – malaria deaths 6 – – topical administration 230–232 – new antiparasitic drugs 15–16 – control of livestock – of horses 5 ectoparasites 236–237 – parasite lifecycle 5 Ehrilichia spp. 276 ® – prevention and control 16–18 Elimax lotion 130 ® – primary ectoparasites of horses 5 Elimax shampoo 130, 131 – principles 170 endoparasiticides 9–10, 256 – prophylaxis 4 epiparasites 3 – Rocky Mountain spotted fever 6 esterases 97, 99, 114, 123, 126 – scabies and head lice 6 European Medicines Agency – screen execution 171 (EMEA) 16, 255 – tick‐borne diseases 5 exploratory dose characterization – ticks 6 studies 277 ® – tungiasis 6 Exspot 230, 233 – viral diseases 6 – whole organism ectoparasite assays 172 f ® ectoparasite efficacy model 224 Famacha 14 ectoparasite infestation 5, 6, 9, 11, 207–209, FAO Working Group on Parasite Resistance 224, 232, 235 (WGPR) 111 ectoparasite models 209–211, 216–218 farm animal vector‐transmitted ectoparasite vaccines 12 pathogens 75 ectoparasiticide discovery and development ferritin 1 (Fer1) 155 – afoxolaner 259 ferritin 2 (Fer2) 156 – artificial feeding system (AFS) 197–198 ferritins 29–30, 155, 156 – control 7–9 fipronil 9, 98, 100, 101, 113, 171, 172, – laboratory animal models testing 174, 175, 180, 182, 184, 194, 198, 213, – – animal and human health 206 215, 216, 228, 229, 231, 232, 246–255, – – bedbugs 216–217 259, 269, 270, 284, 306, 307, 320, – – chemistry optimization 206 326, 327 – – ectoparasite infestation 207–209 flea allergic dermatitis (FAD) 233, 234, – – flea models 215–216 305–307 – – flying insects 217–218 fleas – – lice 217 – artificial feeding systems 191 – – mange mites 218 – contact assay 174–175 – – principal features of 210 – dose confirmation 285–287 – – tick models 211–215 – ectoparasiticide 214–215 – sarolaner discovery 296–299 – efficacy 299–300 – target hosts testing – egg/larval assays 176–177 – – alignment of animal model – ingestion assay 175–176 assays 227–229 – models 215–216 – – discovery campaign 224 – species 276 – – ectoparasiticide products 230 – speed of kill 303–304 – – extension to human conditions 237–238 – topical and oral products 310–312 bindex.indd 355 5/3/2018 2:48:08 PM 356 Index fluazuron 98, 99, 101 host inflammatory and immune fluid‐phase endocytosis (FPE) 143, 147 responses 35–37 flubendiamide 319, 326 host interface 31 fluralaner 198, 235, 248, 249, 251, 252, 254, human head and body lice 255, 295, 297, 310, 312–315, 319, 321, 322, – abametapir‐based formulation 130 324, 325, 330, 332, 339 – benzyl alcohol‐containing fluxametamide 322, 333 formulations 128 fly repellents 5 – dimethicone‐based formamidines 97–98 formulations 128–129 fully engorged female ticks 26, 27, 30, 33, 35 – in vitro rearing system 122 – in vitro louse rearing system 120 g – ivermectin‐based formulations 129–130 GABA‐gated chloride channels (GABA‐Cls) – kdr‐type resistance allele 124 9, 100, 259, 267, 269, 270, 284, 298, 320 – living and feeding behaviors 120 γ‐aminobutyric acid‐gated chloride – malathion resistance 126 channels (GABA-Cls) 247, 251, 252, – metabolic synergists 131 254, 255 – noninvasive induction assay 126–127 ® Gavac 27 – pediculosis 120–121 glutathione S‐transferase (GST) – repellents/deterrents and odorant receptor – esterases 99, 123 discovery 130 – ticks 152–153 – sequencing 123 greyhound 191, 192, 197, 198, 283 – spinosad‐based formulation 130 growth regulators 98–99 – sustainable resistance management 131 – transcriptomes 123 h human vector‐transmitted pathogens 46–63 hard ticks 25, 45, 55, 63, 64, 75, 81, 85, 86, hydroxylated afoxolaner 283 141, 142, 144, 145, 191 hyperparasitism 3 head lice infestations 11 ® HeartGard Plus 280 i heartworm larvae 7 insect growth regulators (IGRs) 170 – prevention 7 insecticide resistance 7, 8, 121–124, 126, ® Hedrin 128 132, 174 helminth infections 4, 6 Insecticide Resistance Action Committee hematophagous

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