Effects of mineral oil administration on the pharmacokinetics, metabolism and pharmacodynamics of atorvastatin and pravastatin in mice and dogs
| Autor: | Hans M.G. Princen, Linnéa Bergenholm, Jonathan Bright, Maria Hammarberg, Eva Lundborg, Elsbet J. Pieterman, Rahul Agrawal, Glen Hawthorne, Annica Jarke, Anders Cavallin, Eva Hurt-Camejo, Bertil Abrahamsson, Rasmus Jansson-Löfmark, V. Sashi Gopaul, Magnus Johansson, Anders Björkbom, Lena Svensson, Xue-Qing Li |
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| Rok vydání: | 2020 |
| Předmět: |
Statin
medicine.drug_class Metabolite Atorvastatin Pharmaceutical Science 02 engineering and technology Pharmacology 030226 pharmacology & pharmacy 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Dogs Pharmacokinetics medicine Animals Mineral Oil Pyrroles cardiovascular diseases Serum amyloid A Mineral oil Pravastatin Chemistry nutritional and metabolic diseases 021001 nanoscience & nanotechnology Mice Inbred C57BL Heptanoic Acids Pharmacodynamics lipids (amino acids peptides and proteins) Hydroxymethylglutaryl-CoA Reductase Inhibitors 0210 nano-technology medicine.drug |
| Zdroj: | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 161 |
| ISSN: | 1879-0720 |
| Popis: | We investigated the effects of mineral oil on statin pharmacokinetics and inflammatory markers in animal models. A new synthesis strategy produced regioisomers that facilitated the characterization of the main metabolite (M1) of atorvastatin, a lipophilic statin, in C57BL/6NCrl mice. The chemical structure of M1 in mice was confirmed as ortho-hydroxy β-oxidized atorvastatin. Atorvastatin and M1 pharmacokinetics and inflammatory markers were assessed in C57BL6/J mice given atorvastatin 5 mg/kg/day or 10 mg/kg/day, as a single dose or for 21 days, with or without 10 µL or 30 µL mineral oil. No consistent differences in plasma exposure of atorvastatin or M1 were observed in mice after single or repeat dosing of atorvastatin with or without mineral oil. However, mice administered atorvastatin 10 mg/kg with 30 µL mineral oil for 21 days had significantly increased plasma levels of serum amyloid A (mean 9.6 µg/mL vs 7.9 µg/mL without mineral oil; p0.01) and significantly increased proportions of C62L |
| Databáze: | OpenAIRE |
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