738b
Tenofovir Pharmacokinetics during Pregnancy, at Delivery and Postpartum
Sandra Burchett*1, B Best2, M Mirochnick3, C Hu4, E Capparelli2, D Holland2, E Smith5, B Sheeran6, J Read7, A Stek8, and PACTG P1026s Team
1Children's Hosp Boston, MA, US; 2Univ of California, Los Angeles, Sch of Med, US; 3Boston Univ, MA, US; 4Harvard Sch of Publ Hlth, Boston, MA, US; 5NIAID, NIH, Bethesda, MD, US; 6Social & Sci Systems, Silver Spring, MD, US; 7Natl Inst of Child Hlth and Human Devt, NIH, Bethesda, MD, US; and 8Univ of Southern California, Los Angeles, US
Background: Tenofovir (TDF), a once-daily nucleotide
reverse transcriptase inhibitor (NRTI), is a frequent component of HAART
regimens but no data are available
describing the pharmacokinetics of TDF with chronic dosing during pregnancy. As
part of the P1026s protocol, TDF
pharmacokinetics was studied in pregnant women during the third trimester, at
delivery and postpartum.
Methods: P1026s is an ongoing, prospective,
non-blinded study of antiretroviral pharmacokinetics in HIV-1-infected pregnant
women receiving antiretrovirals for routine clinical care,
including a cohort receiving 300 mg TDF daily, either as Viread or
co-formulated with emtricitabine (Truvada). Intensive steady-state TDF
pharmacokinetics profiles were performed at 30 to 36 weeks’ gestation (third
trimester) and 6 to 12 weeks’ postpartum. TDF concentrations were assessed by
liquid chromatography/mass spectroscopy. The target
TDF AUC24 was ≥2
µg*h/mL (10th percentile of non-pregnant historical controls). Third
trimester and postpartum pharmacokinetics parameters
were compared by the Wilcoxon signed
rank test.
Results: As of December 2006, 19 women (4 black, 7
Hispanic, 6 white; median age 30.5 years,
median weight 80.1 kg) had been studied during the third trimester, and 14
postpartum. TDF AUC exceeded the target
for 14 of the 19 (74%; 95%CI 49 to 91%) third trimester women and for 12 of 14
(86%; 95%CI 57 to 98%) postpartum women. TDF AUC, Clast and Cmax
were lower during the third trimester compared
to postpartum (p = 0.020, 0.064 and
0.069, respectively), but third trimester Cmin and C0
were not different from postpartum values. The median maternal : cord
concentrations at delivery were 65:62 ng/mL with a median ratio of 1.04 (range
0.6 to 1.7). Of 16 third trimester women, 14 and of 10 postpartum women, 7 had
an HIV viral load ≤400 copies/mL.
|
Time (n)
|
TDF AUC (µg*hr/mL)
Median (range)
|
TDF C0 (ng/mL)
Median (range)
|
TDF C24 (ng/mL)
Median (range)
|
TDF CMax (ng/mL)
Median (range)
|
|
third trimester (19)
|
2.5 (1.1–3.6)
|
53.7 (15.1–104)
|
55.4 (27.5–119)
|
245.0 (146–483)
|
|
PP (14)
|
2.95 (1.6–7.2)
|
67.1 (<10–135)
|
113.7 (26.4–125)
|
309.5 (134–739)
|
Conclusions: TDF AUC, Clast and Cmax
were lower during the third trimester than in the same women postpartum.
Chronic dosing with TDF results in umbilical cord blood concentrations at least
60% of maternal concentrations.
|
