Involvement of breast cancer resistance protein (BCRP/ABCG2) in the secretion of danofloxacin into milk: interaction with ivermectin
| Autor: | R, Real, E, Egido, M, Pérez, L, González-Lobato, B, Barrera, J G, Prieto, A I, Alvarez, G, Merino |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Ivermectin Sheep Antiparasitic Agents Drug Administration Schedule Anti-Bacterial Agents Neoplasm Proteins Mice Milk ATP Binding Cassette Transporter Subfamily G Member 2 Animals Humans ATP-Binding Cassette Transporters Drug Interactions Female Cells Cultured Chromatography High Pressure Liquid Fluoroquinolones |
| Zdroj: | Journal of veterinary pharmacology and therapeutics. 34(4) |
| ISSN: | 1365-2885 |
| Popis: | Danofloxacin, a veterinary fluoroquinolone antimicrobial drug, is actively secreted into milk by an as yet unknown mechanism. One of the main determinants of active drug secretion into milk is the transporter (BCRP/ABCG2). The main purpose was to determine whether danofloxacin is an in vitro substrate for Bcrp1/BCRP and to assess its involvement in danofloxacin secretion into milk. In addition, the role of potential drug-drug interactions in this process was assessed using ivermectin. Danofloxacin was transported in vitro by Bcrp1/BCRP, and ivermectin efficiently blocked this transport. Experiments with Bcrp1(-/-) mice showed no evidence of the involvement of Bcrp1 in plasma pharmacokinetics of danofloxacin. However, the milk concentration and milk-to-plasma ratio of danofloxacin were almost twofold higher in wild-type compared with Bcrp1(-/-) mice. The in vivo interaction with ivermectin was studied in sheep after co-administration of danofloxacin (1.25 mg/kg, i.m.) and ivermectin (0.2 mg/kg, s.c.). Ivermectin had no significant effect on the plasma levels of danofloxacin but significantly decreased danofloxacin concentrations in milk by almost 40%. Concomitant administration of multiple drugs, often used in veterinary therapy, may not only affect their pharmacological activity but also their secretion into milk, because of potential drug-drug interactions mediated by BCRP. |
| Databáze: | OpenAIRE |
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