Norbert Mencke , Wolfgang Bäumer , Kristine Fraatz , Ralph Krebber , Marc Schneider , Katrin Blazejak
{"title":"局部给药组合产品(Felpreva®)和单独活性成分静脉给药后替戈兰那、emodepside和吡喹酮在猫体内的血浆药代动力学","authors":"Norbert Mencke , Wolfgang Bäumer , Kristine Fraatz , Ralph Krebber , Marc Schneider , Katrin Blazejak","doi":"10.1016/j.crpvbd.2023.100126","DOIUrl":null,"url":null,"abstract":"<div><p>Felpreva® for cats contains the new acaricidal/insecticidal active ingredient tigolaner in a fixed combination with the nematocidal and cestocidal compounds emodepside and praziquantel, respectively. The plasma pharmacokinetics of tigolaner, emodepside, and praziquantel were evaluated in clinically healthy cats following topical (spot-on) treatment as fixed combination Felpreva®. For the determination of bioavailability intravenous administration of single active ingredients was also performed. After a single topical administration of Felpreva® using the target dose volume of 0.148 ml/kg to cats, tigolaner reached mean peak concentrations of 1352 μg/l with a T<sub>max</sub> of 12 days and a mean half-life of 24 days. Simulation of repetitive topical administration every 91 days indicates only a low risk of accumulation after reaching steady state within two to three administrations. The volume of distribution calculated after intravenous dosing was 4 l/kg and plasma clearance was low with 0.005 l/h/kg. Overall plasma exposure was 1566 mg∗h/l after topical administration, providing an absolute bioavailability of 57%. Tigolaner was mainly cleared <em>via</em> the faeces (54% within 28 days), renal clearance was neglectable (< 0.5% within 28 days). Emodepside and praziquantel showed mean peak concentrations of 44 μg/l and 48 μg/l (reached after 1.5 days and 5 h, respectively). Overall plasma exposures were 20.6 and 3.69 mg∗h/l, respectively. The elimination half-life was 14.5 days for emodepside and 10 days for praziquantel after topical administration. After topical administration of Felpreva® using 2.5× and 5× dose multiples an almost proportional increase of plasma exposure was observed for all three active ingredients. With the addition of tigolaner, Felpreva® combines the established pharmacokinetic (PK) characteristics of emodepside and praziquantel contained in Profender® spot-on for cats with the favourable PK of tigolaner suitable for a 3-months protection against fleas and ticks.</p></div>","PeriodicalId":94311,"journal":{"name":"Current research in parasitology & vector-borne diseases","volume":"4 ","pages":"Article 100126"},"PeriodicalIF":1.7000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10344656/pdf/","citationCount":"0","resultStr":"{\"title\":\"Plasma pharmacokinetics of tigolaner, emodepside, and praziquantel following topical administration of a combination product (Felpreva®) and of intravenous administration of the individual active ingredients in cats\",\"authors\":\"Norbert Mencke , Wolfgang Bäumer , Kristine Fraatz , Ralph Krebber , Marc Schneider , Katrin Blazejak\",\"doi\":\"10.1016/j.crpvbd.2023.100126\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Felpreva® for cats contains the new acaricidal/insecticidal active ingredient tigolaner in a fixed combination with the nematocidal and cestocidal compounds emodepside and praziquantel, respectively. The plasma pharmacokinetics of tigolaner, emodepside, and praziquantel were evaluated in clinically healthy cats following topical (spot-on) treatment as fixed combination Felpreva®. For the determination of bioavailability intravenous administration of single active ingredients was also performed. After a single topical administration of Felpreva® using the target dose volume of 0.148 ml/kg to cats, tigolaner reached mean peak concentrations of 1352 μg/l with a T<sub>max</sub> of 12 days and a mean half-life of 24 days. Simulation of repetitive topical administration every 91 days indicates only a low risk of accumulation after reaching steady state within two to three administrations. The volume of distribution calculated after intravenous dosing was 4 l/kg and plasma clearance was low with 0.005 l/h/kg. Overall plasma exposure was 1566 mg∗h/l after topical administration, providing an absolute bioavailability of 57%. Tigolaner was mainly cleared <em>via</em> the faeces (54% within 28 days), renal clearance was neglectable (< 0.5% within 28 days). Emodepside and praziquantel showed mean peak concentrations of 44 μg/l and 48 μg/l (reached after 1.5 days and 5 h, respectively). Overall plasma exposures were 20.6 and 3.69 mg∗h/l, respectively. The elimination half-life was 14.5 days for emodepside and 10 days for praziquantel after topical administration. After topical administration of Felpreva® using 2.5× and 5× dose multiples an almost proportional increase of plasma exposure was observed for all three active ingredients. With the addition of tigolaner, Felpreva® combines the established pharmacokinetic (PK) characteristics of emodepside and praziquantel contained in Profender® spot-on for cats with the favourable PK of tigolaner suitable for a 3-months protection against fleas and ticks.</p></div>\",\"PeriodicalId\":94311,\"journal\":{\"name\":\"Current research in parasitology & vector-borne diseases\",\"volume\":\"4 \",\"pages\":\"Article 100126\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10344656/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current research in parasitology & vector-borne diseases\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2667114X23000146\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PARASITOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current research in parasitology & vector-borne diseases","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2667114X23000146","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PARASITOLOGY","Score":null,"Total":0}
Plasma pharmacokinetics of tigolaner, emodepside, and praziquantel following topical administration of a combination product (Felpreva®) and of intravenous administration of the individual active ingredients in cats
Felpreva® for cats contains the new acaricidal/insecticidal active ingredient tigolaner in a fixed combination with the nematocidal and cestocidal compounds emodepside and praziquantel, respectively. The plasma pharmacokinetics of tigolaner, emodepside, and praziquantel were evaluated in clinically healthy cats following topical (spot-on) treatment as fixed combination Felpreva®. For the determination of bioavailability intravenous administration of single active ingredients was also performed. After a single topical administration of Felpreva® using the target dose volume of 0.148 ml/kg to cats, tigolaner reached mean peak concentrations of 1352 μg/l with a Tmax of 12 days and a mean half-life of 24 days. Simulation of repetitive topical administration every 91 days indicates only a low risk of accumulation after reaching steady state within two to three administrations. The volume of distribution calculated after intravenous dosing was 4 l/kg and plasma clearance was low with 0.005 l/h/kg. Overall plasma exposure was 1566 mg∗h/l after topical administration, providing an absolute bioavailability of 57%. Tigolaner was mainly cleared via the faeces (54% within 28 days), renal clearance was neglectable (< 0.5% within 28 days). Emodepside and praziquantel showed mean peak concentrations of 44 μg/l and 48 μg/l (reached after 1.5 days and 5 h, respectively). Overall plasma exposures were 20.6 and 3.69 mg∗h/l, respectively. The elimination half-life was 14.5 days for emodepside and 10 days for praziquantel after topical administration. After topical administration of Felpreva® using 2.5× and 5× dose multiples an almost proportional increase of plasma exposure was observed for all three active ingredients. With the addition of tigolaner, Felpreva® combines the established pharmacokinetic (PK) characteristics of emodepside and praziquantel contained in Profender® spot-on for cats with the favourable PK of tigolaner suitable for a 3-months protection against fleas and ticks.