Division of Oral and Maxillofacial Surgery, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
PLoS One. 2021 Feb 18;16(2):e0246994. doi: 10.1371/journal.pone.0246994. eCollection 2021.
Therapeutic drug monitoring (TDM) is used in certain clinically selected cases and in research settings to optimize the response to antiretroviral therapy. Plasma of blood is commonly used for TDM, but blood sampling is invasive and at risk for transmission of infectious agents. On the other hand, saliva sampling is noninvasive, safe, cheap, and easily performed compared to blood. Dolutegravir (DTG) is now widely prescribed as a key component of antiretroviral therapy for HIV infection. In this study, we examined the relationship between DTG concentrations in plasma and saliva of treated patients to explore the possibility of using saliva as an alternative body fluid of TDM. A total of 17 pairs of blood and saliva samples were obtained from 15 consented HIV-1-infected subjects treated with DTG containing regimens for more than one month. Both blood and saliva samples were collected within 1 h of each other. Drug concentrations were determined by liquid chromatography-tandem mass spectrometry using DTG-d5 as an internal standard. The LLOQ was 0.5 ng/mL. The calibration curves were prepared with pooled plasma or saliva containing DTG in a range of 0.5-100 ng/mL with precision of <14.4% and accuracy within ±14.7%. The DTG concentrations in the plasma and saliva were significantly correlated (Pearson's correlation coefficient r = 0.76, p < 0.001). The median ratio of the drug concentration in saliva to those in plasma was 0.0056, which is close to the rate of non-protein-bound DTG in plasma (0.70%), suggesting that only free DTG in plasma is transported to the salivary glands and secreted into saliva. The present study demonstrates that DTG concentration in saliva reflects the pharmacologically active drug concentration in plasma and may provide an easily accessible alternative for monitoring effective antiretroviral treatment.
治疗药物监测（TDM）用于某些临床选定的病例和研究环境中，以优化对抗逆转录病毒治疗的反应。通常使用血浆进行 TDM，但血液采样具有侵入性，并且有传播感染性病原体的风险。另一方面，与血液相比，唾液采样是非侵入性的、安全的、廉价的，并且易于操作。多替拉韦（DTG）现在广泛用作 HIV 感染抗逆转录病毒治疗的关键组成部分。在这项研究中，我们研究了治疗患者的血浆和唾液中的 DTG 浓度之间的关系，以探索使用唾液作为 TDM 替代体液的可能性。总共从 15 名接受 DTG 治疗方案治疗超过一个月的 HIV-1 感染患者中获得了 17 对血液和唾液样本。在彼此 1 小时内采集了血液和唾液样本。使用 DTG-d5 作为内标，通过液相色谱-串联质谱法测定药物浓度。LLOQ 为 0.5ng/mL。校准曲线使用包含 DTG 的混合血浆或唾液制备，范围为 0.5-100ng/mL，精度 <14.4%，准确度在 ±14.7%范围内。血浆和唾液中的 DTG 浓度呈显著相关（Pearson 相关系数 r=0.76，p<0.001）。药物浓度在唾液中的中位数与在血浆中的比值为 0.0056，接近血浆中非蛋白结合 DTG 的比率（0.70%），表明只有游离 DTG 血浆被转运到唾液腺并分泌到唾液中。本研究表明，唾液中的 DTG 浓度反映了血浆中具有药理活性的药物浓度，并且可能为监测有效的抗逆转录病毒治疗提供一种易于获得的替代方法。
