Pharmacokinetics
DTG is rapidly absorbed from the gastrointestinal tract (median time to maximum concentration [Tmax]: 2.1 hours) after oral administration of 50 mg under fasting conditions. The presence of food increases the extent and slows the rate of DTG absorption. A low-fat meal (300 kcal, 7% fat) increases DTG bioavailability by 33%, while a moderate-fat (600 kcal, 30% fat) and high-fat (870 kcal, 53% fat) meal increase bioavailability by 41% and 66%, respectively; Tmax is extended to 3, 4, and 5 hours, respectively, and suggests that DTG displays solubility-limited absorption.13 Administration of DTG with food is not required for INSTI-naïve patients but should be employed in patients with INSTI class resistance.11,14 The apparent volume of distribution (Vd/F) in HIV-infected subjects is 17–20 L based on population pharmacokinetics.11 DTG is greater than 99% bound to plasma proteins in a concentration-independent fashion.11 Distribution into the cerebrospinal fluid (CSF) and the male and female genital tract is evident; CSF concentrations (median: 18 ng/mL, range: 4–232 ng/mL) are similar to unbound serum concentrations (16.8 ng/mL); semen, rectal, and cervicovaginal tissue concentrations are 7%, 17%, and 7%–10% of steady-state serum concentrations.15–1
PharmacokineticsDTG is rapidly absorbed from the gastrointestinal tract (median time to maximum concentration [Tmax]: 2.1 hours) after oral administration of 50 mg under fasting conditions. The presence of food increases the extent and slows the rate of DTG absorption. A low-fat meal (300 kcal, 7% fat) increases DTG bioavailability by 33%, while a moderate-fat (600 kcal, 30% fat) and high-fat (870 kcal, 53% fat) meal increase bioavailability by 41% and 66%, respectively; Tmax is extended to 3, 4, and 5 hours, respectively, and suggests that DTG displays solubility-limited absorption.13 Administration of DTG with food is not required for INSTI-naïve patients but should be employed in patients with INSTI class resistance.11,14 The apparent volume of distribution (Vd/F) in HIV-infected subjects is 17–20 L based on population pharmacokinetics.11 DTG is greater than 99% bound to plasma proteins in a concentration-independent fashion.11 Distribution into the cerebrospinal fluid (CSF) and the male and female genital tract is evident; CSF concentrations (median: 18 ng/mL, range: 4–232 ng/mL) are similar to unbound serum concentrations (16.8 ng/mL); semen, rectal, and cervicovaginal tissue concentrations are 7%, 17%, and 7%–10% of steady-state serum concentrations.15–1
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