Urinary excretion of l-carnitine and its short-chain acetyl-l-carnitine in patients undergoing carboplatin treatment

Mancinelli, Angelo; D'Iddio, S; Bisonni, Renato; Graziano, Francesco; Lippe, P.; Calvani, Menotti

doi:10.1007/s00280-006-0341-3

Cited by 22 publications

(15 citation statements)

References 29 publications

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“…In this context, it is particularly noteworthy that, in a previous study involving a small cohort of adult patients, treatment with cisplatin was associated with a significant increase in the urinary excretion of carnitine, which eventually normalized about 7 days after discontinuing therapy (Heuberger et al, 1998). Similar observations have been made in patients undergoing combination chemotherapy with ifosfamide-doxorubicin-cisplatin (Hockenberry et al, 2009), paclitaxel-carboplatin, or vinorelbine-carboplatin (Mancinelli et al, 2007). In the case of cisplatin treatment, the increases in urinary carnitine were hypothesized to be due to inhibition of active tubular reabsorption of carnitine and acylcarnitines (Heuberger et al, 1998), and direct inhibition of OCTN2 has been reported for several oncology drugs, including actinomycin D (Ohashi et al, 1999), vinblastine (Diao et al, 2009), and etoposide .…”

Section: Platinum Chemotherapeuticssupporting

confidence: 63%

Uptake Carriers and Oncology Drug Safety

Sprowl

Sparreboom

2013

Drug Metab Dispos

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Members of the solute carrier (SLC) family of transporters are responsible for the cellular influx of a broad range of endogenous compounds and xenobiotics in multiple tissues. Many of these transporters are highly expressed in the gastrointestinal tract, liver, and kidney and are considered to be of particular importance in governing drug absorption, elimination, and cellular sensitivity of specific organs to a wide variety of oncology drugs. Although the majority of studies on the interaction of oncology drugs with SLC have been restricted to the use of exploratory in vitro model systems, emerging evidence suggests that several SLCs, including OCT2 and OATP1B1, contribute to clinically important phenotypes associated with those agents. Recent literature has indicated that modulation of SLC activity may result in drug-drug interactions, and genetic polymorphisms in SLC genes have been described that can affect the handling of substrates. Alteration of SLC function by either of these mechanisms has been demonstrated to contribute to interindividual variability in the pharmacokinetics and toxicity associated with several oncology drugs. In this report, we provide an update on this rapidly emerging field.

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Section: Platinum Chemotherapeuticssupporting

confidence: 63%

Uptake Carriers and Oncology Drug Safety

Sprowl

Sparreboom

2013

Drug Metab Dispos

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“…Previous research has shown that while serum carnitine levels remained stable throughout treatment, urinary excretion was significantly elevated [8,25]. Considering that most participants were well nourished, and adequate dietary carnitine intake throughout chemotherapy treatment appeared sufficient to prevent deficiency.…”

Section: Page 3 Ofmentioning

confidence: 87%

“…Multiple studies have evaluated carnitine status in oncology patients undergoing chemotherapy using serum and/or urinary markers of carnitine [4][5][6][7][8][9][10][11]. While not all studies found that chemotherapy resulted in carnitine deficiency, all studies found carnitine metabolism to be significantly impaired during the study period.…”

Section: Introductionmentioning

confidence: 99%

“…cisplatin), and ifosfamide have been shown to disrupt regular carnitine metabolism. Several potential mechanisms have been proposed including an increased rate of renal excretion [5,8] a reduction in cellular uptake [12] and an increase in the metabolic demand for carnitine [13] therefore, prolonged exposure to these regimens may result in carnitine deficiencies [7]. In addition, most studies to date have only measured the acute changes in carnitine status during chemotherapy rather than over the course of multiple cycles which is typical of most chemotherapy regimens.…”

Section: Introductionmentioning

confidence: 99%

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The Effect of Chemotherapy on Serum Carnitine Levels and Fatigue in Chemotherapy Naive Medical Oncology Patients: A Pilot Study. Carnitine, Chemotherapy and Fatigue

Marx

Teleni

Ferguson

et al. 2013

J Nutr Disorders Ther

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Background: Fatigue, a highly prevalent side-effect of anticancer therapy, poses a significant burden on patient quality of life. Carnitine deficiency has been implicated in the development of fatigue during chemotherapy.Methods: This pilot study aimed to evaluate the relationship between chemotherapy-related fatigue and serum carnitine (total, free-and acyl: free carnitine ratio) in 35 chemotherapy-naïve oncology patients at baseline, 6 and12 weeks.Results: Carnitine deficiency, based on acyl: free carnitine ratio, was detected in three patients at baseline but this did not persist to the next time point. Carnitine deficiency was not detected in any other participant throughout this study and levels of carnitine were not correlated with fatigue during the study period. Conclusion:A relationship between carnitine status and fatigue was not found at the time points measured. Further research is required to confirm these results in a larger medical oncology population.

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“…Patients with cancer have decreased activity of mitochondrial carnitine O-palmitoyltransferase 1 and 2 (CPT-1 and CPT-2), enzymes that belong to the 'carnitine system' and are responsible for β-oxidation of LCFA (8,9). Moreover, the consequences and complications of cancer treatment such as chemotherapy, radiotherapy and surgical procedures can also contribute to a decrease in LC (10)(11)(12)(13). This study was designed to assess the influence of CC on LC distribution and metabolic pathways.…”

Section: Introductionmentioning

confidence: 99%

L-carnitine and cancer cachexia. I. L-carnitine distribution and metabolic disorders in cancer cachexia

Szefel¹,

Kruszewski

Ciesielski

et al. 2012

Oncol Rep

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Abstract. Cancer cachexia (CC), a progressive loss of body mass, is associated with decreased energy production. Abnormally low levels of L-carnitine (LC) in skeletal muscle means that mitochondrial β-oxidation of long-chain fatty acids (LCFA) does not occur efficiently in patients with CC. We assessed the influence of CC on LC distribution and the effects of parenteral lipid emulsions on plasma LC levels and urinary excretion. Fifty patients with CC were randomly assigned to total parenteral nutrition (TPN) with long-chain triglycerides (LCTs), or LCTs plus medium-chain triglycerides (MCTs) as 50/50. Patients were further separated into those with body-mass index (BMI) ≤19 kg/m 2 and BMI >19 kg/m 2 . Plasma concentrations of total LC (TC) and free LC (FC) and their urinary excretion were measured, along with skeletal muscle LC levels. On average, plasma FC and TC were higher than reference values in all patients. Patients with BMI ≤19 kg/m 2 had lower plasma FC and TC than those with BMI >19 kg/m 2 . Skeletal muscle FC in the BMI ≤19 kg/m 2 group was lower than reference value, but within the normal range in others. LC and FC urinary excretion was higher than reference values. Plasma LC and its urinary excretion were higher in patients administered pure LCTs relative to those given MCTs/LCTs. A decrease in skeletal muscle LC in cancer patients with CC (BMI ≤19 kg/m 2 ) correlates with an increase in its plasma levels and increased renal excretion. A diet of MCTs/LCTs reduces LC release from muscle to plasma and urine more effectively than LCTs.

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Urinary excretion of l-carnitine and its short-chain acetyl-l-carnitine in patients undergoing carboplatin treatment

Abstract: Treatment with carboplatin was associated with a marked urinary loss of LC and ALC, most likely due to inhibition of carnitine reabsorption in the kidney.

Cited by 22 publications

References 29 publications

Uptake Carriers and Oncology Drug Safety

Uptake Carriers and Oncology Drug Safety

The Effect of Chemotherapy on Serum Carnitine Levels and Fatigue in Chemotherapy Naive Medical Oncology Patients: A Pilot Study. Carnitine, Chemotherapy and Fatigue

L-carnitine and cancer cachexia. I. L-carnitine distribution and metabolic disorders in cancer cachexia

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