Impact on L-carnitine Homeostasis of Short-term Treatment with the Pivalate Prodrug Tenofovir Dipivoxil Impact on L-carnitine Level of Tenofovir Dipivoxil
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.
Tenofovir dipivoxil carnitine hepatitis B herpes simplex virus hypocarnitinemia
Yan-Yan Jia Tai-Jun Hang Cheng-Tao Lu Juan Feng Ying Song Jin-Yi Zhao Shan Wang Yuan Sun Ai-Dong Wen Zhi-Fu Yang
Department of Pharmacy,Xijing Hospital,Fourth Military Medical University,Xi”an,710038,P. R. China Department of Pharmaceutical Analysis,China Pharmaceutical University,Nanjing 210009,PR China
国内会议
南宁
英文
1-17
2013-11-01（万方平台首次上网日期，不代表论文的发表时间）