Dolutegravir pharmacokinetics in pregnant and postpartum women living with HIV

To evaluate dolutegravir pharmacokinetics during pregnancy compared with postpartum and in infant washout samples after delivery. Ongoing, nonrandomized, open-label, parallel-group, multicenter phase-IV prospective study of antiretroviral pharmacokinetics in HIV-infected pregnant women and infants....

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	AIDS (London) Ročník 32; číslo 6; s. 729
Hlavní autoři:	Mulligan, Nikki, Best, Brookie M, Wang, Jiajia, Capparelli, Edmund V, Stek, Alice, Barr, Emily, Buschur, Shelley L, Acosta, Edward P, Smith, Elizabeth, Chakhtoura, Nahida, Burchett, Sandra, Mirochnick, Mark
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	England 27.03.2018
Témata:	Adult Chromatography, Liquid Female Heterocyclic Compounds, 3-Ring - administration & dosage Heterocyclic Compounds, 3-Ring - pharmacokinetics HIV - isolation & purification HIV Infections - drug therapy HIV Integrase Inhibitors - administration & dosage HIV Integrase Inhibitors - pharmacokinetics Humans Infant, Newborn Male Oxazines Piperazines Plasma - chemistry Postpartum Period Pregnancy Pregnancy Complications, Infectious - drug therapy Prospective Studies Pyridones Tandem Mass Spectrometry Viral Load Young Adult
ISSN:	1473-5571, 1473-5571
On-line přístup:	Zjistit podrobnosti o přístupu
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	To evaluate dolutegravir pharmacokinetics during pregnancy compared with postpartum and in infant washout samples after delivery. Ongoing, nonrandomized, open-label, parallel-group, multicenter phase-IV prospective study of antiretroviral pharmacokinetics in HIV-infected pregnant women and infants. Intensive steady-state 24 h pharmacokinetic profiles after dolutegravir 50 mg once-daily were performed during the second trimester (2T), third trimester (3T) and postpartum. Maternal delivery and postnatal infant samples were collected after birth. Dolutegravir was measured by validated LC-MS/MS; quantitation limit was 0.005 μg/ml. A two-tailed Wilcoxon signed-rank test (α = 0.10) was employed for paired within-subject comparisons. Twenty-nine enrolled participants had a median age of 32 years (range 21-42). Pharmacokinetic data were available for 15 (2T), 28 (3T) and 23 (postpartum) women. Median dolutegravir AUC0-24,Cmax and C24 were 25-51% lower in the 2T and 3T compared with postpartum. The median cord blood/maternal plasma concentration ratio was 1.25 (n = 18). In 21 infants, median elimination half-life was 32.8 h after in utero exposure. Viral load at delivery was less than 50 copies/ml for 27/29 women (93%). Twenty-nine infants were HIV-negative. Renal abnormalities noted on ultrasound in two infants were deemed possibly related to dolutegravir. Dolutegravir exposure is lower in pregnancy compared with postpartum in the same women on once-daily dosing. Median AUC0-24 during pregnancy was similar to, whereas trough concentrations were lower than, those seen in nonpregnant adults. Trough concentrations in pregnancy were well above dolutegravir EC90 (0.064 μg/ml). Dolutegravir readily crosses the placenta. Infant elimination is prolonged, with half-life over twice that of historical adult controls.
Bibliografie:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	1473-5571 1473-5571
DOI:	10.1097/QAD.0000000000001755