When nutrients and drugs share the same absorption and disposition mechanisms, significant interactions between the two substances can occur. Because these processes undergo ontogenesis throughout the postnatal period, the outcomes of drug-nutrient interactions may change with postnatal age during development. Cefepime-carnitine, a significant drug-nutrient interaction, was found to be dependent on drug exposure timing and duration in relation to postnatal age in our study. Cefepime (5 mg/kg) was given to rat pups twice daily by subcutaneous injection on various dosing schedules. In the postnatal day 1-4, 1-8, and 8-11 groups, cefepime caused severe degenerative changes in the ventricular myocardium and significantly reduced serum and heart L-carnitine levels. Additionally, the ontogeny of a number of important L-carnitine homeostasis pathways was altered by cefepime. The time and duration of exposure to cefepime affected the qualitative and quantitative changes in hepatic -butyrobetaine hydroxylase mRNA and activity, hepatic trimethyllysine hydroxlase mRNA, intestinal organic cation/carnitine transporter (Octn) mRNA, and renal Octn2 mRNA. With cefepime exposure, all treatment groups maintained the same levels of ATP, carnitine palmitoyltransferase mRNA and activity, heart Octn2 mRNA, and lower levels of heart L-carnitine. However, rats with normal serum L-carnitine levels showed changes in other high energy phosphate substrates and decreased phosphocreatine/ATP ratios. In conclusion, our findings point to a significant drug-nutrient transport interaction in developing neonates, whose nature is affected by exposure timing and duration in relation to postnatal age.
Share this article