Pivalate-generating prodrugs have been suggested to cause clinically significant hypocarnitinemia.Tenofovir dipivoxil,a novel ester prodrug of tenofovir,can be used for treatment of hepatitis B and HIV infection and it was necessary to evaluate the effect of its treatment on carnitine homeostasis.We sought to investigate the effect of Class 1 drug tenofovir dipivoxil on endogenous L-carnitine level during a 72-h test in healthy Chinese volunteers and to establish a suitable dose of L-carnitine nutritional supplement for patients who were administrated with short-term tenofovir dipivoxil tablets for treatment of hepatitis B and herpes simplex virus infection.Tenofovir dipivoxil was administered in one of eight dosing regimens (single-dose 150 mg,300 mg and 600 mg,multi-dose 300 mg,450 mg,and 600 mg,multi-dose 450 (600) mg tenofovir dipivoxil and 0.5g L-carnitine) to gender-balanced groups of 84 healthy Chinese volunteers.Plasma concentrations of L-carnitine were quantified before,during,and after treatment.Plasma L-carnitine concentrations fell during tenofovir dipivoxil dosing.The nadir in L-carnitine concentration was dependent on the dose of tenofovir dipivoxil and it decreased from 6.1±0.6 to 4.4±0.8 μg/ml,6.1±1.8 to 3.3±1.2 μg/ml,6.2±0.6 to 2.5±0.5 μg/ml for single doses of 150,300,600 mg tenofovir dipivoxil tablets and from 6.0±1.4 to 2.1±1.5 μg/ml,6.2±0.4 to 0.9±0.5 μg/ml for multiple doses of 450,600 mg tenofovir dipivoxil tablets,respectively.Short-term administration of tenofovir dipivoxil results in hypocarnitinemia and increased losses of carnitine in resulting of minor adverse events of decreased food appetite,nausea,abdominal distention and muscle weakness.