Carnitine Levels Decrease during Oxaliplatin Infusion: A Pilot Study

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect of chemotherapy. Low carnitine levels might negatively affect the development of CIPN. However, little is known of the course of carnitine levels during and directly after chemotherapy administration. Intervention studies using carnitine to prevent CIPN were contradictory, possibly due to different timing and route of carnitine supplementation. Better understanding of carnitine courses might improve future studies. This study aimed to investigate whether oxaliplatin-based chemotherapy administration affects blood and urinary levels of carnitine. We hypothesized that oxaliplatin increases renal excretion of carnitine, thereby causing a carnitine deficiency, which might contribute to the development of CIPN.

Ten patients, starting their first cycle of oxaliplatin-based chemotherapy, were enrolled in this observational pilot study. Blood and urinary samples were taken before, during and after infusion of oxaliplatin. Primary endpoints were changes in plasma and urinary concentrations of free carnitine and carnitine esters during administration of oxaliplatin-based chemotherapy.

This study showed a significant decrease of both free carnitine and carnitine esters in plasma 2 h after the start of infusion of oxaliplatin-based chemotherapy. Moreover, a non-significant increase in urine carnitine concentration was seen during the chemotherapy infusion.

The altered plasma and urinary concentrations of carnitine support our hypothesis that oxaliplatin causes increased renal excretion of carnitine, thereby lowering blood-carnitine levels and increasing urinary carnitine levels. With continued loss of carnitine over several chemotherapy cycles, this may result in the development of carnitine deficiency, which could contribute to the development of CIPN. These preliminary results provide a basis for hypothesis generation; larger longitudinal studies are required to confirm these findings and to determine the clinical relevance.