SYSTEMIC EFFICACY OF NODULISPORAMIDES AGAINST FLEAS ON DOGS
Nodulisporic acid A (NSA) has been shown previously to be safe in dogs and to deliver >90% flea control for 4 days following a single oral administration. Three newly prepared nodulisporamide derivatives were subsequently identified from an artificial membrane flea feeding system as exhibiting po...
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| Veröffentlicht in: | The Journal of parasitology 2001-10, Vol.87 (5), p.1150-1154 |
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| creator | Shoop, W. L Zakson-Aiken, M Gregory, L. M Michael, B. F Pivnichny, J Meinke, P. T Fisher, M. H Wyvratt, M. J Pikounis, B Schmatz, D. M |
| description | Nodulisporic acid A (NSA) has been shown previously to be safe in dogs and to deliver >90% flea control for 4 days following a single oral administration. Three newly prepared nodulisporamide derivatives were subsequently identified from an artificial membrane flea feeding system as exhibiting potency substantially greater than NSA. To determine if they have superior in vivo activity, these 3 nodulisporamides, as well as NSA, were evaluated in dogs at 15 mg/kg/os. Parasite challenges were made by placing 100 live Ctenocephalides felis fleas onto the dorsum of dogs every 48 hr and examining efficacy at each of those intervals over a 22-day period. Results showed that NSA produced >90% efficacy at day 2 and 81% efficacy at day 4, and its residual flea killing fell to ∼50% by day 6 posttreatment. All dogs treated with the 3 new experimental nodulisporamides were 100% protected from flea challenges to day 8 posttreatment, and 2 of the compounds continued to produce >90% residual activity to 2 wk posttreatment. Pharmacokinetic analysis showed that plasma profiles and half-lives of NSA and these 3 new compounds correlated closely with flea efficacy. These results demonstrate that specific substitutions to the pharmacophore of NSA can substantially increase the duration of activity against fleas. |
| doi_str_mv | 10.1645/0022-3395(2001)087[1150:SEONAF]2.0.CO;2 |
| format | Article |
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L ; Zakson-Aiken, M ; Gregory, L. M ; Michael, B. F ; Pivnichny, J ; Meinke, P. T ; Fisher, M. H ; Wyvratt, M. J ; Pikounis, B ; Schmatz, D. M</creator><creatorcontrib>Shoop, W. L ; Zakson-Aiken, M ; Gregory, L. M ; Michael, B. F ; Pivnichny, J ; Meinke, P. T ; Fisher, M. H ; Wyvratt, M. J ; Pikounis, B ; Schmatz, D. M</creatorcontrib><description>Nodulisporic acid A (NSA) has been shown previously to be safe in dogs and to deliver >90% flea control for 4 days following a single oral administration. Three newly prepared nodulisporamide derivatives were subsequently identified from an artificial membrane flea feeding system as exhibiting potency substantially greater than NSA. To determine if they have superior in vivo activity, these 3 nodulisporamides, as well as NSA, were evaluated in dogs at 15 mg/kg/os. Parasite challenges were made by placing 100 live Ctenocephalides felis fleas onto the dorsum of dogs every 48 hr and examining efficacy at each of those intervals over a 22-day period. Results showed that NSA produced >90% efficacy at day 2 and 81% efficacy at day 4, and its residual flea killing fell to ∼50% by day 6 posttreatment. All dogs treated with the 3 new experimental nodulisporamides were 100% protected from flea challenges to day 8 posttreatment, and 2 of the compounds continued to produce >90% residual activity to 2 wk posttreatment. Pharmacokinetic analysis showed that plasma profiles and half-lives of NSA and these 3 new compounds correlated closely with flea efficacy. These results demonstrate that specific substitutions to the pharmacophore of NSA can substantially increase the duration of activity against fleas.</description><identifier>ISSN: 0022-3395</identifier><identifier>EISSN: 1937-2345</identifier><identifier>DOI: 10.1645/0022-3395(2001)087[1150:SEONAF]2.0.CO;2</identifier><identifier>PMID: 11695382</identifier><identifier>CODEN: JOPAA2</identifier><language>eng</language><publisher>Lawrence, KS: American Society of Parasitologists</publisher><subject>Acids ; Administration, Oral ; Aluminum ; Amides ; Amides - blood ; Amides - pharmacokinetics ; Amides - pharmacology ; Animals ; Artificial membranes ; Biological and medical sciences ; Blood ; Blood plasma ; Dog Diseases - drug therapy ; Dog Diseases - metabolism ; Dog Diseases - parasitology ; Dogs ; Ectoparasites ; Fleas ; General pharmacology ; Half lives ; Half-Life ; In vivo methods and tests ; Indoles - blood ; Indoles - pharmacokinetics ; Indoles - pharmacology ; Insecticides - blood ; Insecticides - pharmacokinetics ; Insecticides - pharmacology ; Male ; Medical sciences ; Natural products ; Oral administration ; Parasitology ; Pharmacognosy. Homeopathy. Health food ; Pharmacokinetics ; Pharmacology ; Pharmacology. Drug treatments ; Plasma ; Random Allocation ; Siphonaptera ; Sleeves ; THERAPEUTICS–DIAGNOSTICS</subject><ispartof>The Journal of parasitology, 2001-10, Vol.87 (5), p.1150-1154</ispartof><rights>American Society of Parasitologists</rights><rights>Copyright 2001 American Society of Parasitologists</rights><rights>2002 INIST-CNRS</rights><rights>Copyright Allen Press Inc. Oct 2001</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b490t-d4728048e2d13294b62f51e38787a166a3f67237237124de815399dab558dde3</citedby><cites>FETCH-LOGICAL-b490t-d4728048e2d13294b62f51e38787a166a3f67237237124de815399dab558dde3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://bioone.org/doi/pdf/10.1645/0022-3395(2001)087[1150:SEONAF]2.0.CO;2$$EPDF$$P50$$Gbioone$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3285249$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,780,784,803,26976,27922,27923,52361,58015,58248</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14146125$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11695382$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shoop, W. L</creatorcontrib><creatorcontrib>Zakson-Aiken, M</creatorcontrib><creatorcontrib>Gregory, L. M</creatorcontrib><creatorcontrib>Michael, B. F</creatorcontrib><creatorcontrib>Pivnichny, J</creatorcontrib><creatorcontrib>Meinke, P. T</creatorcontrib><creatorcontrib>Fisher, M. H</creatorcontrib><creatorcontrib>Wyvratt, M. J</creatorcontrib><creatorcontrib>Pikounis, B</creatorcontrib><creatorcontrib>Schmatz, D. M</creatorcontrib><title>SYSTEMIC EFFICACY OF NODULISPORAMIDES AGAINST FLEAS ON DOGS</title><title>The Journal of parasitology</title><addtitle>J Parasitol</addtitle><description>Nodulisporic acid A (NSA) has been shown previously to be safe in dogs and to deliver >90% flea control for 4 days following a single oral administration. Three newly prepared nodulisporamide derivatives were subsequently identified from an artificial membrane flea feeding system as exhibiting potency substantially greater than NSA. To determine if they have superior in vivo activity, these 3 nodulisporamides, as well as NSA, were evaluated in dogs at 15 mg/kg/os. Parasite challenges were made by placing 100 live Ctenocephalides felis fleas onto the dorsum of dogs every 48 hr and examining efficacy at each of those intervals over a 22-day period. Results showed that NSA produced >90% efficacy at day 2 and 81% efficacy at day 4, and its residual flea killing fell to ∼50% by day 6 posttreatment. All dogs treated with the 3 new experimental nodulisporamides were 100% protected from flea challenges to day 8 posttreatment, and 2 of the compounds continued to produce >90% residual activity to 2 wk posttreatment. Pharmacokinetic analysis showed that plasma profiles and half-lives of NSA and these 3 new compounds correlated closely with flea efficacy. These results demonstrate that specific substitutions to the pharmacophore of NSA can substantially increase the duration of activity against fleas.</description><subject>Acids</subject><subject>Administration, Oral</subject><subject>Aluminum</subject><subject>Amides</subject><subject>Amides - blood</subject><subject>Amides - pharmacokinetics</subject><subject>Amides - pharmacology</subject><subject>Animals</subject><subject>Artificial membranes</subject><subject>Biological and medical sciences</subject><subject>Blood</subject><subject>Blood plasma</subject><subject>Dog Diseases - drug therapy</subject><subject>Dog Diseases - metabolism</subject><subject>Dog Diseases - parasitology</subject><subject>Dogs</subject><subject>Ectoparasites</subject><subject>Fleas</subject><subject>General pharmacology</subject><subject>Half lives</subject><subject>Half-Life</subject><subject>In vivo methods and tests</subject><subject>Indoles - blood</subject><subject>Indoles - pharmacokinetics</subject><subject>Indoles - pharmacology</subject><subject>Insecticides - blood</subject><subject>Insecticides - pharmacokinetics</subject><subject>Insecticides - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Natural products</subject><subject>Oral administration</subject><subject>Parasitology</subject><subject>Pharmacognosy. Homeopathy. Health food</subject><subject>Pharmacokinetics</subject><subject>Pharmacology</subject><subject>Pharmacology. 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Homeopathy. Health food</topic><topic>Pharmacokinetics</topic><topic>Pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Plasma</topic><topic>Random Allocation</topic><topic>Siphonaptera</topic><topic>Sleeves</topic><topic>THERAPEUTICS–DIAGNOSTICS</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shoop, W. L</creatorcontrib><creatorcontrib>Zakson-Aiken, M</creatorcontrib><creatorcontrib>Gregory, L. M</creatorcontrib><creatorcontrib>Michael, B. F</creatorcontrib><creatorcontrib>Pivnichny, J</creatorcontrib><creatorcontrib>Meinke, P. T</creatorcontrib><creatorcontrib>Fisher, M. H</creatorcontrib><creatorcontrib>Wyvratt, M. J</creatorcontrib><creatorcontrib>Pikounis, B</creatorcontrib><creatorcontrib>Schmatz, D. 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To determine if they have superior in vivo activity, these 3 nodulisporamides, as well as NSA, were evaluated in dogs at 15 mg/kg/os. Parasite challenges were made by placing 100 live Ctenocephalides felis fleas onto the dorsum of dogs every 48 hr and examining efficacy at each of those intervals over a 22-day period. Results showed that NSA produced >90% efficacy at day 2 and 81% efficacy at day 4, and its residual flea killing fell to ∼50% by day 6 posttreatment. All dogs treated with the 3 new experimental nodulisporamides were 100% protected from flea challenges to day 8 posttreatment, and 2 of the compounds continued to produce >90% residual activity to 2 wk posttreatment. Pharmacokinetic analysis showed that plasma profiles and half-lives of NSA and these 3 new compounds correlated closely with flea efficacy. These results demonstrate that specific substitutions to the pharmacophore of NSA can substantially increase the duration of activity against fleas.</abstract><cop>Lawrence, KS</cop><pub>American Society of Parasitologists</pub><pmid>11695382</pmid><doi>10.1645/0022-3395(2001)087[1150:SEONAF]2.0.CO;2</doi><tpages>5</tpages></addata></record> |
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| language | eng |
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| subjects | Acids Administration, Oral Aluminum Amides Amides - blood Amides - pharmacokinetics Amides - pharmacology Animals Artificial membranes Biological and medical sciences Blood Blood plasma Dog Diseases - drug therapy Dog Diseases - metabolism Dog Diseases - parasitology Dogs Ectoparasites Fleas General pharmacology Half lives Half-Life In vivo methods and tests Indoles - blood Indoles - pharmacokinetics Indoles - pharmacology Insecticides - blood Insecticides - pharmacokinetics Insecticides - pharmacology Male Medical sciences Natural products Oral administration Parasitology Pharmacognosy. Homeopathy. Health food Pharmacokinetics Pharmacology Pharmacology. Drug treatments Plasma Random Allocation Siphonaptera Sleeves THERAPEUTICS–DIAGNOSTICS |
| title | SYSTEMIC EFFICACY OF NODULISPORAMIDES AGAINST FLEAS ON DOGS |
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