| Title | Acute administration of cefepime lowers L-carnitine concentrations in early lactation stage rat milk. | | Author(s) | Ling B, Alcorn J | | Institution | College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, S7N 5C9 Canada. | | Source | J Nutr 2008 Jul; 138(7):1317-22. | | Abstract | Our study investigated the potential for important in vivo drug-nutrient transport interactions at the lactating mammary gland using the l-carnitine transporter substrates, cefepime and l-carnitine, as proof-of-concept. On d 4 (n = 6/treatment) and d 10 (n = 6/treatment) of lactation, rats were administered cefepime (250 mg/h) or saline by continuous i.v. infusion (4 h). Serum and milk l-carnitine and cefepime concentrations were quantified by HPLC-UV. In whole mammary gland, organic cation/carnitine transporter (OCTN)1, OCTN2, OCTN3, amino acid transporter B(0,+) (ATB(0,+)), and l-carnitine transporter 2 expression were determined by quantitative RT-PCR and by western blot and immunohistochemistry when possible. Cefepime caused a 56% decrease in milk l-carnitine concentrations on lactation d 4 (P = 0.0048) but did not affect milk l-carnitine at lactation d 10 or serum l-carnitine concentrations at either time. The mean l-carnitine and cefepime milk:serum ratios (M/S) decreased from 9.1 +/- 0.4 to 4.9 +/- 0.6 (P < 0.0001) and 0.89 +/- 0.3 to 0.12 +/- 0.02 (P = 0.0473), respectively, between d 4 and d 10 of lactation. In both groups, OCTN2 (P < 0.0001), OCTN3 (P = 0.0039), and ATB(0,+) (P = 0.004) mRNA expression and OCTN2 protein (P < 0.0001) were higher in mammary glands at d 4 of lactation compared with d 10. Immunohistochemistry revealed OCTN1 and OCTN2 localization in the mammary alveolar epithelium and OCTN3 expression in the interstitial space and blood vessel endothelium. In conclusion, cefepime significantly decreased milk l-carnitine concentrations only at d 4 of lactation. Relative to d 10, enhanced expression of OCTN2 and ATB(0,+) in mammary glands at d 4 of lactation and higher M/S (l-carnitine and cefepime) suggests cefepime competes with l-carnitine for l-carnitine transporters expressed in the lactating mammary gland to adversely affect l-carnitine milk concentrations and these effects depend upon lactation stage. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 18567754 |
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