Raltegravir Is Safe with No Dosage Changes Needed during Pregnancy

		SUMMARY: HIV positive women can safely take the integrase inhibitor raltegravir (Isentress) during pregnancy and do not need to have their dosages adjusted to account for changes in size or blood volume, according to study results presented this month at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010) in Boston.

By Liz Highleyman

B.M. Best from the University of California San Diego and colleagues looked at raltegravir pharmacokinetic data for pregnant women with HIV in their third trimester, comparing it with previously obtained historical data for non-pregnant individuals.

Raltegravir displays marked absorption and disposition variability in non-pregnant adults, the researchers noted as background, but information about raltegravir pharmacokinetics during pregnancy has not been available.

This analysis included pharmacokinetic data from 10 women in the IMPAACT P1026s study, collected from the third trimester of pregnancy until 6 weeks after delivery (post-partum). Maternal blood plasma samples were collected before dosing and at 1, 2, 4, 6, 8, and 12 hours after dosing. Umbilical cord blood and maternal blood were also collected at the time of delivery.

Pregnant Women took the standard adult dose of 400 mg twice-daily. In non-pregnant adults, the target 12-hour raltegravir concentration (C12h), or minimum therapeutic level (estimated 10th percentile), is > 35 ng/mL, with a median of 63 ng/mL.

Results

	Raltegravir pharmacokinetic parameters varied greatly among study participants.
	None of the parameters were significantly different between pregnant women and historical non-pregnant adults.
	Raltegravir concentrations also did not differ between the third trimester and post-partum:
	Area under the curve (AUC), or total concentration over the dosing interval: median 8.3 mcg x hr/mL third trimester vs 7.5 mcg x hr/mL post-partum; Pre-dose concentration (C-pre-dose): median 85 ng/mL third trimester vs 496 mg/mL post-partum; 12-hour concentration (C12h): median 107 ng/mL third trimester vs 77 mg/mL post-partum. Maximum concentration (Cmax): median 1775 ng/mL third trimester vs 2760 mg/mL post-partum. Drug clearance (CL/F): median 50 L/hr third trimester vs 54 L/hr post-partum.
	All 10 of 10 women reached the C12h target during the third trimester, and 5 of 6 did so post-partum.
	Raltegravir readily crossed the placenta.
	Based on 6 deliveries, the median concentration of raltegravir in cord blood was 125 ng/mL.
	The median raltegravir concentration in post-partum maternal plasma was 145 ng/mL (range 28-626 ng/mL).
	The median raltegravir concentration ratio of cord blood to maternal blood was 1.20.

"Consistent with previous reports, raltegravir pharmacokinetics showed extensive variability," the study investigators concluded. "Raltegravir exposure was not consistently altered during third trimester compared to post-partum and historical data, and the standard dose appears appropriate during pregnancy."

Investigator affiliations: Univ. of California, San Diego, La Jolla, CA; Univ. of Southern California, Los Angeles, CA; Children's Hosp. Boston, Boston, MA; Harvard School of Public Health, Boston, MA; Univ. of California, San Francisco, San Francisco, CA; NIAID, Bethesda, MD; NICHD, Bethesda, MD; Boston Univ., Boston, MA.

9/28/10

Reference
BM Best, EV Capparelli, A Stek, and others. Raltegravir Pharmacokinetics during Pregnancy. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010). Boston, September 12-15, 2010. Abstract H-1668a.