Timing and Duration of Drug Exposure Affects Outcomes of a Drug-Nutrient Interaction During Ontogeny 英文参考文献.docVIP

Pharmaceutics 2010, 2, 321-338; doi:10.3390/pharmaceutics2040321 OPEN ACCESS Pharmaceutics ISSN 1999-4923 /journal/pharmaceutics Article Timing and Duration of Drug Exposure Affects Outcomes of a Drug-Nutrient Interaction During Ontogeny Binbing Ling 1, Caroline Aziz 2, Chris Wojnarowicz 3, Andrew Olkowski 4 and Jane Alcorn 1,* 1 College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, S7N5C9, Canada 2 Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK, S7N 5B3, Canada 3 Department of Veterinary Pathology, Prairie Diagnostic Services, 52 Campus Drive, University of Saskatchewan, Saskatoon, SK, S7N 5B4, Canada 4 Department of Animal and Poultry Science, University of Saskatchewan, 51 Campus Drive Saskatoon, SK, S7N 5A8, Canada * Author to whom correspondence should be addressed; E-Mail: jane.alcorn@usask.ca; Tel.: 1-306-966-6365. Received: 9 September 2010; in revised form: 5 October 2010 / Accepted: 12 October 2010 / Published: 14 October 2010 Abstract: Significant drug-nutrient interactions are possible when drugs and nutrients share the same absorption and disposition mechanisms. During postnatal development, the outcomes of drug-nutrient interactions may change with postnatal age since these processes undergo ontogenesis through the postnatal period. Our study investigated the dependence of a significant drug-nutrient interaction (cefepime-carnitine) on the timing and duration of drug exposure relative to postnatal age. Rat pups were administered cefepime (5 mg/kg) twice daily subcutaneously according to different dosing schedules (postnatal day 1-4, 1-8, 8-11, 8-20, or 1-20). Cefepime significantly reduced serum and heart L-carnitine levels in postnatal day 1-4, 1-8 and 8-11 groups and caused severe degenerative changes in ventricular myocardium in these groups. Cefepime also altered the ontogeny of several key L-carnitine homeostasis pathways. T