Lowe Selwyn H, van Leeuwen Elisabeth, Droste Jacqueline A H, van der Veen Fulco, Reiss Peter, Lange Joep M A, Burger David M, Repping Sjoerd, Prins Jan M
Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Ther Drug Monit. 2007 Oct;29(5):566-70. doi: 10.1097/FTD.0b013e31811fef29.
Data on the concentrations of didanosine (ddI) and tenofovir (TFV) in seminal plasma are sparse. Subtherapeutic drug concentrations within the lumen of the male genital tract may have implications for selection and transmission of drug-resistant HIV strains. On the other hand, sufficient penetration of these drugs into the male genital tract has potential toxic effects on the spermatozoa and their precursors. In the current study, the authors obtained paired semen and blood samples at variable time points after drug intake from 30 HIV-1-infected patients using a ddI (n = 15) or ddI + TFV (n = 15) containing an antiretroviral regimen. Didanosine and TFV concentrations were measured in seminal and blood plasma and semen quality was assessed. Both ddI and TFV penetrated well into seminal plasma. Whereas blood plasma ddI concentrations dropped to near or below the lower limit of quantification of 0.017 microg/mL 9 hours after drug intake, the ddI concentration in seminal plasma remained detectable during the whole dosing interval with a median of 0.20 and 0.21 microg/mL in the ddI and ddI + TFV groups, respectively. Tenofovir was detectable during the whole dosing interval in both blood and seminal plasma with a median concentration of 0.12 and 0.25 microg/mL, respectively, and a median seminal-to-blood-plasma ratio of 3.3. Semen quality was within the normal range according to the criteria of the World Health Organization, except for the percentage of progressively motile sperm, which was low in both groups of patients. The authors conclude that ddI and TFV penetrate well into seminal plasma and that the reduced sperm motility deserves further study.
关于去羟肌苷（ddI）和替诺福韦（TFV）在精浆中的浓度数据稀少。男性生殖道管腔内低于治疗剂量的药物浓度可能对耐药性HIV毒株的选择和传播有影响。另一方面，这些药物充分渗透到男性生殖道对精子及其前体有潜在毒性作用。在本研究中，作者从30例感染HIV-1的患者中，在服用含ddI（n = 15）或ddI + TFV（n = 15）的抗逆转录病毒方案后的不同时间点采集了配对的精液和血液样本。测定了精液和血浆中去羟肌苷和替诺福韦的浓度，并评估了精液质量。ddI和TFV均能很好地渗透到精浆中。服药9小时后血浆中ddI浓度降至接近或低于定量下限0.017μg/mL，而在整个给药间隔期间精浆中的ddI浓度仍可检测到，ddI组和ddI + TFV组的中位数分别为0.20和0.21μg/mL。替诺福韦在整个给药间隔期间在血液和精浆中均可检测到，中位数浓度分别为0.12和0.25μg/mL，精浆与血浆的中位数比值为3.3。根据世界卫生组织的标准，精液质量在正常范围内，但两组患者的进行性运动精子百分比均较低。作者得出结论，ddI和TFV能很好地渗透到精浆中，精子活力降低值得进一步研究。
