Vourvahis Manoli, Tappouni Hiba L, Patterson Kristine B, Chen Ya-Chi, Rezk Naser L, Fiscus Susan A, Kearney Brian P, Rooney James F, Hui James, Cohen Myron S, Kashuba Angela D M
Division of Pharmacotherapy and Experimental Therapeutics, School of Pharmacy, University of North Carolina, Chapel Hill , NC 27599-7360, USA.
J Acquir Immune Defic Syndr. 2008 Mar 1;47(3):329-33. doi: 10.1097/QAI.0b013e3181632cc3.
To measure tenofovir (TFV) concentrations in the male genital tract (GT) after single and multiple doses of tenofovir disoproxil fumarate (TDF) and evaluate the HIV-1 RNA response to monotherapy.
A pharmacokinetic study of blood plasma (BP) and GT TFV concentrations in 9 men was conducted after 1 and > or =14 doses of TDF. TFV concentrations were measured by validated high-performance liquid chromatography-ultraviolet or tandem mass spectrometry methods, and HIV-1 RNA was measured using Roche (Roche Molecular Systems, Branchburg, NJ) or bioMerieux (bioMerieux, Durham, NC) kits.
TFV GT concentrations were 4.4-fold +/- 5.1-fold higher than BP after dose 1 and 5.1-fold +/- 6.8-fold higher than BP after dose 14. Intracellular GT TFV-diphosphate concentrations were 9.4-fold higher than BP after dose 1 and 17.5-fold +/- 22.6-fold higher after dose 7. After 14 days ofTDF monotherapy, HIV-1 RNA decreased by 0.9 log10 copies/mL in blood and 1.0 log10 copies/mL in the GT.
High TFV concentrations were achieved rapidly in the GT of all subjects after single and multiple doses and potently reduced BP and GT HIV-1 RNA levels.
测量单次和多次服用富马酸替诺福韦二吡呋酯（TDF）后男性生殖道（GT）中的替诺福韦（TFV）浓度，并评估HIV-1 RNA对单一疗法的反应。
对9名男性在服用1剂和≥14剂TDF后进行血浆（BP）和GT中TFV浓度的药代动力学研究。通过经过验证的高效液相色谱-紫外或串联质谱法测量TFV浓度，使用罗氏公司（新泽西州布兰奇堡罗氏分子系统公司）或生物梅里埃公司（北卡罗来纳州达勒姆生物梅里埃公司）的试剂盒测量HIV-1 RNA。
第1剂后GT中TFV浓度比BP高4.4倍±5.1倍，第14剂后比BP高5.1倍±6.8倍。细胞内GT中TFV二磷酸浓度在第1剂后比BP高9.4倍，第7剂后高17.5倍±22.6倍。TDF单一疗法14天后，血液中HIV-1 RNA下降0.9 log10拷贝/毫升，GT中下降1.0 log10拷贝/毫升。
所有受试者在单次和多次给药后GT中迅速达到高TFV浓度，并有效降低BP和GT中的HIV-1 RNA水平。
