Pharmacokinetics and Dolutegravir in HIV Treatment Research
Quinn Heutmaker
University of Minnesota Duluth
Abstract
Dolutegravir (DTG) is the fourth integrase inhibitor approved by the Food and Drug Administration for use in HIV treatment at a dosage of 50 mg PO once daily (FDA, 2018). This review addresses research into the safety and pharmacokinetics of DTG. Using clinical trials with healthy subjects for pharmacokinetic investigation of DTG, research has observed the primary metabolic pathway and the primary elimination pathway as fecal elimination (Castellino et al. 2013). This same research observed the half-life and absorption rate to be approximately 15 hours and .5 -1.25 hours, respectively (Castellino et al. 2013). Other research tested the efficacy of DTG tested in HIV-positive adults, finding it to lower HIV-RNA concentrations in the blood (Letendre et al. 2014; Min et al. 2011) and cerebrospinal fluid (Letendre et al. 2014), while increasing the subjects’ CD4 counts (Letendre et al. 2014), which was also observed in HIV-positive adolescents (Viani et al. 2015). DTG was also observed to pass through the placenta in HIV-positive pregnant women with an initially low concentration that rose over time (Mulligan et al. 2018). Several studies then tested the safety of DTG coadministration with other treatment drugs for HIV (Anderson et al. 2017; Ford et al. 2013), Hepatitis C (Johnson et al. 2014; Khatri et al. 2016; Ross et al. 2016), and other HIV side effects (Song et al. 2013), and only coadministration with carbamazepine was deemed unsafe (Song et al. 2013). However, these coadministration experiments were only done with healthy subjects, and women were underrepresented in DTG testing overall, having either tight requirements to meet for participation (Song et al. 2013; Ross et al. 2016) or being excluded altogether (Castellino et al. 2013).
