Upprepad administrering av trimetoprim/sulfadiazin till neonatala föl
Today most dosages used in horse medicine are based on studies in adult horses. Since there are differences between adult and neonatal horses with respect to different pharmacological parameters this can cause problems when administring drugs to neonatal foals. Neonatal sepsis is a common cause of m...
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| Format: | Otro |
| Language: | Swedish Swedish |
| Published: |
2009
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| Online Access: | https://stud.epsilon.slu.se/11799/ |
| _version_ | 1855571941784551424 |
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| author | Arnljot, Anna-Karin |
| author_browse | Arnljot, Anna-Karin |
| author_facet | Arnljot, Anna-Karin |
| author_sort | Arnljot, Anna-Karin |
| collection | Epsilon Archive for Student Projects |
| description | Today most dosages used in horse medicine are based on studies in adult horses. Since there are differences between adult and neonatal horses with respect to different pharmacological parameters this can cause problems when administring drugs to neonatal foals. Neonatal sepsis is a common cause of morbidity and mortality in foals and aggressive antibiotic treatment is needed immediately when sepsis is suspected. In Sweden the combination of trimethoprim/sulphadiazine and bensylpenicillin is often used as the initial treatment. When administering drugs, interactions can occur between the drugs and endogenous substances. An example of such an interaction is called "displacement" and refers in this case to the competition for binding places on plasma proteins between drugs and highly protein-bound enogenous substances. Drugs that themselves are highly protein-bound are at a greater risk for displacement. Bilirubin is an example of an endogenous substance that to a great extent (>99 %) is bound to albumin. When displacement occur more free unconjugated bilirubin becomes available systemically and to a greater extent can pass the blood-brain barrier and cause cellular damage, so called kernicterus. Kernicterus has mostly been reported in neonatal children and is rarely seen in animals. Kernicterus in foals in association with trimethoprim/sulfadiazine treatment has not been reported but it is theoretically possible that also foals could be affected. The aims of the study were to evaluate the dosage used today and its safety with respect to displacement of bilirubin.
Seven healthy foals were treated with trimethoprim/sulfadiazine, 15 mg/kg q 12 h for three days. Blood samples were taken daily at the same time points during four days and the concentrations of total protein, albumin and bilrubin (total, conjugated, unconjugated and free unconjugated) were analysed in plasma. Blood samples were taken at the same time points in a matched control group with seven healthy foals. No differences in levels between the different parameters were seen betweeen the foals treated with trimetoprim/sulfadiazin and the controls. The concentration of free unconjugated bilirubin was analysed with equilibrium dialysis and no differences were seen between the foals treated with trimetoprim/sulfadiazin and the control group. The protein binding was 23 % for trimethoprim and 14 % for sulfadiazine, which is a bit lower than the protein binding measured in adult horses at 35 % and 20% respectively. The results in this study, and the clinical experience without reported cases of kernicterus associated with treatment of trimethoprim/sulfadiazin, implies that the dosage used today does not seem to enhance the risk of kernicterus in neonatal foals. One should, however, consider that this study was performed on clinically healthy foals. Since it is known that many diseases affect the turnover of different endogenous and exogenous substances, further studies are warranted in which focus should be put on septicaemic foals, younger neonatal and prenatal foals. |
| format | Otro |
| id | RepoSLU11799 |
| institution | Swedish University of Agricultural Sciences |
| language | Swedish swe |
| publishDate | 2009 |
| publishDateSort | 2009 |
| record_format | eprints |
| spelling | RepoSLU117992017-10-17T07:01:06Z https://stud.epsilon.slu.se/11799/ Upprepad administrering av trimetoprim/sulfadiazin till neonatala föl Arnljot, Anna-Karin Veterinary science and hygiene - General aspects Today most dosages used in horse medicine are based on studies in adult horses. Since there are differences between adult and neonatal horses with respect to different pharmacological parameters this can cause problems when administring drugs to neonatal foals. Neonatal sepsis is a common cause of morbidity and mortality in foals and aggressive antibiotic treatment is needed immediately when sepsis is suspected. In Sweden the combination of trimethoprim/sulphadiazine and bensylpenicillin is often used as the initial treatment. When administering drugs, interactions can occur between the drugs and endogenous substances. An example of such an interaction is called "displacement" and refers in this case to the competition for binding places on plasma proteins between drugs and highly protein-bound enogenous substances. Drugs that themselves are highly protein-bound are at a greater risk for displacement. Bilirubin is an example of an endogenous substance that to a great extent (>99 %) is bound to albumin. When displacement occur more free unconjugated bilirubin becomes available systemically and to a greater extent can pass the blood-brain barrier and cause cellular damage, so called kernicterus. Kernicterus has mostly been reported in neonatal children and is rarely seen in animals. Kernicterus in foals in association with trimethoprim/sulfadiazine treatment has not been reported but it is theoretically possible that also foals could be affected. The aims of the study were to evaluate the dosage used today and its safety with respect to displacement of bilirubin. Seven healthy foals were treated with trimethoprim/sulfadiazine, 15 mg/kg q 12 h for three days. Blood samples were taken daily at the same time points during four days and the concentrations of total protein, albumin and bilrubin (total, conjugated, unconjugated and free unconjugated) were analysed in plasma. Blood samples were taken at the same time points in a matched control group with seven healthy foals. No differences in levels between the different parameters were seen betweeen the foals treated with trimetoprim/sulfadiazin and the controls. The concentration of free unconjugated bilirubin was analysed with equilibrium dialysis and no differences were seen between the foals treated with trimetoprim/sulfadiazin and the control group. The protein binding was 23 % for trimethoprim and 14 % for sulfadiazine, which is a bit lower than the protein binding measured in adult horses at 35 % and 20% respectively. The results in this study, and the clinical experience without reported cases of kernicterus associated with treatment of trimethoprim/sulfadiazin, implies that the dosage used today does not seem to enhance the risk of kernicterus in neonatal foals. One should, however, consider that this study was performed on clinically healthy foals. Since it is known that many diseases affect the turnover of different endogenous and exogenous substances, further studies are warranted in which focus should be put on septicaemic foals, younger neonatal and prenatal foals. Idag bygger de flesta doseringsangivelser inom hästmedicinen på data från vuxna hästar. Detta kan skapa problem då läkemedelsomsättningen hos neonatala föl kan skilja sig från omsättningen hos vuxna hästar. Neonatal sepsis är en vanlig anledning till morbiditet och mortalitet hos föl och kräver snabbt insatt antibiotikabehandling. I Sverige används ofta kombinationen trimetoprim/sulfadiazin tillsammans med bensylpenicillin. Vid användning av läkemedel kan interaktioner mellan läkemedlen och endogena substanser inträffa. Ett exempel på detta är så kallad ”displacement” där det uppstår en konkurrenssituation mellan läkemedlet och endogena substanser om bindningplatser på plasmaproteiner. Detta gäller framför allt endogena substanser med hög proteinbindningsgrad och risken för displacement är större vid användning av ett läkemedel som själv har hög proteinbindningsgrad. Bilirubin är ett exempel på en endogen substans med hög proteinbindningsgrad, > 99 %. Vid displacement innebär detta att fritt okonjugerat bilirubin i större utsträckning riskerar att passera blodhjärnbarriären och orsaka skada, så kallad kernikterus. Kernikterus har framförallt rapporterats på neonatala barn och är väldigt sällsynt hos djur. Kernikterus på föl i samband med trimetoprimsulfabehandling finns inte rapporterat men teoretiskt är det fullt möjligt att föl skulle kunna drabbas. Denna studie syftar till att undersöka om den nuvarande doseringen för trimetoprim/sulfadiazin är säker att använda för neonatala föl med avseende på displacement av bilirubin. Sju kliniskt friska varmblodiga travarföl injicerades intravenöst med trimetoprim/sulfadiazin i doseringen 15 mg/kg q 12 h under tre dagar. Blodprov togs dagligen vid samma tidpunkt i fyra dagar och koncentrationen totalprotein, albumin och bilirubin (totalt, konjugerat, okonjugerat samt fritt okonjugerat) i plasma analyserades. Blodprov togs vid samma tidpunkter hos en matchad kontrollgrupp på sju friska föl. Inga skillnader i nivåer av de olika parametrarna kunde ses mellan fölen som behandlats med trimetoprim/sulfadiazin och kontrollgruppen. Koncentrationen fritt okonjugerat bilirubin analyserades med hjälp av jämviktsdialys och inte heller där sågs några skillnader mellan fölen som behandlats med trimetoprim/sulfadiazin och kontrollgruppen. Proteinbindningsgraden uppmättes till 23 % för trimetoprim och 14 % för sulfadiazine, vilket är lägre än proteinbindningsgraden för vuxna hästar på 35 % respektive 20 %. Resultaten i denna studie, samt den kliniska erfarenheten med avsaknad av rapporterade fall av kernikterus på föl i samband med trimetoprim/sulfadiazinbehandling, tyder på att den dosering av trimetoprim/sulfadiazin som idag används inte ökar risken för kernikterus hos neonatala föl. Denna studie har dock utförts på kliniskt friska föl. Eftersom man vet att diverse sjukdomstillstånd påverkar omsättningen av olika substanser bör vidare studier utföras där man fokuserar på föl sjuka i sepsis, och gärna även yngre neonatala samt prenatala föl. 2009-02-24 Other NonPeerReviewed application/pdf sv https://stud.epsilon.slu.se/11799/1/arnljot_a_171017.pdf Arnljot, Anna-Karin, 2009. Upprepad administrering av trimetoprim/sulfadiazin till neonatala föl : plasmaproteinbindning och effekt på serumbilirubinkoncentrationen. UNSPECIFIED, Uppsala. Uppsala: (VH) > Dept. of Clinical Sciences (until 231231) <https://stud.epsilon.slu.se/view/divisions/OID-715.html> urn:nbn:se:slu:epsilon-s-7890 swe |
| spellingShingle | Veterinary science and hygiene - General aspects Arnljot, Anna-Karin Upprepad administrering av trimetoprim/sulfadiazin till neonatala föl |
| title | Upprepad administrering av trimetoprim/sulfadiazin till neonatala föl |
| title_full | Upprepad administrering av trimetoprim/sulfadiazin till neonatala föl |
| title_fullStr | Upprepad administrering av trimetoprim/sulfadiazin till neonatala föl |
| title_full_unstemmed | Upprepad administrering av trimetoprim/sulfadiazin till neonatala föl |
| title_short | Upprepad administrering av trimetoprim/sulfadiazin till neonatala föl |
| title_sort | upprepad administrering av trimetoprim/sulfadiazin till neonatala föl |
| topic | Veterinary science and hygiene - General aspects |
| url | https://stud.epsilon.slu.se/11799/ https://stud.epsilon.slu.se/11799/ |