Urinary excretion of L-carnitine and its short-chain acetyl-L-carnitine in patients undergoing carboplatin treatment.
OBJECTIVE
To evaluate the effect of the anti-cancer drug carboplatin on plasma concentrations and urinary excretion of L-carnitine (LC) and its main ester, acetyl-L-carnitine (ALC), in cancer patients.


METHODS
Plasma and urine concentrations of LC and ALC from 11 patients on carboplatin therapy (1 h intravenous infusion; AUC dose 4.8 +/- 1.1 mg/ml min) in combination with docetaxel, paclitaxel or vinorelbine, were determined by high-performance liquid chromatography with fluorimetric detection.


RESULTS
Before carboplatin therapy, the mean +/- SD plasma concentrations of LC and ALC were 47.8 +/- 10.9 and 7.04 +/- 1.04 nmoles/ml, respectively, and remained constant throughout the entire study period. In contrast, urinary excretion of LC and ALC, increased significantly during the chemotherapy from 115 +/- 105 to 480 +/- 348 micromoles/day (P < 0.01) and from 41 +/- 41 to 89 +/- 52 micromoles/day (P < 0.05) for LC and ALC, respectively, subsequently reverting to normal 6 days after the end of chemotherapy. Similarly, the renal clearance of LC and ALC increased substantially during chemotherapy from 1.67 +/- 1.43 to 9.05 +/- 9.52 ml/min (P < 0.05) and from 4.02 +/- 4.51 to 7.97 +/- 5.05 ml/min (P = not significant) for LC and ALC, respectively, reverting to normal 6 days after the end of chemotherapy. Plasma concentrations and urinary excretion of glucose, phosphate and urea nitrogen and creatinine clearance, however, were not affected by carboplatin therapy, indicating no impaired kidney function.


CONCLUSIONS
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.
Mancinelli
Angelo
A
Scientific Department, Sigma-Tau, Via Pontina Km 30,400, Pomezia, Italy. angelo.mancinelli@sigma-tau.it
D'Iddio
S
S
Bisonni
R
R
Graziano
F
F
Lippe
P
P
Calvani
M
M
D000108:Acetylcarnitine / Q000652:urine*; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002331:Carnitine / Q000652:urine*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003404:Creatinine / Q000652:urine; D000077143:Docetaxel; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000652:urine; D017239:Paclitaxel / Q000008:administration & dosage; D010710:Phosphates / Q000652:urine; D043823:Taxoids / Q000008:administration & dosage; D014508:Urea / Q000652:urine; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
D000970:Antineoplastic Agents; D010710:Phosphates; D043823:Taxoids; D000077143:Docetaxel; D014747:Vinblastine; D000108:Acetylcarnitine; D014508:Urea; D003404:Creatinine; D016190:Carboplatin; D005947:Glucose; D017239:Paclitaxel; D000077235:Vinorelbine; D002331:Carnitine