Raltegravir pharmacokinetics inpregnancy
1 October 2010. Related: Conference reports, Antiretrovirals, Pregnancy, ICAAC 50th Boston 2010.
Polly Clayden, HIV i-Base
Raltegravir shows variability in absorption and disposition in non-pregnant adults. Additionally the physiological changes associated with pregnancy may have an effect on drug disposition and decreased plasma concentrations have been observed with some protease inhibitors.
Edmund Capparelli and colleagues showed results from a study to determine the pharmacokinetics (PK) of raltegravir in the third trimester of pregnancy and compare these to postpartum PK data in the same women and to historical controls.
Women were enrolled in IMPAACT P1025 and its PK substudy and receiving 400 mg raltegravir twice daily in combination regimens. At the time of the evaluation all women had been on two weeks or more of stable therapy.
The investigators performed PK evaluations during the third trimester and 6-12 weeks post partum. Samples were collected pre-dose and 1, 2, 4, 6, 8 and 12 hours post dose. Cord blood and maternal samples were collected at delivery.
The target trough concentration was 35ng/mL (this is the target trough concentration in non-pregnant adults).
Ten pregnant women completed the third trimester evaluation and six the postpartum PK. Women were a median of 20.9 years (range 20.035.4) and weighed a median of 79.6 kg (range 61.4120.7) in the third trimester.
The investigators reported highly variable PK but these were not significantly different between pregnancy and post partum. The cord blood and maternal plasma concentrations were similar indicating that raltegravir crosses the placenta.
Raltegravir pharmacokinetics in pregnancy are shown in Table 1 and plasma concentrations at delivery shown in Table 2.
Table1: Raltegravir pharmacokinetics in pregnancy and postpartum, median (range)
| Parameter | Third trimester (n=10) | Postpartum (n=6) |
| AUC (mcg*hr/mL) | 8.3 (3.017.5) | 7.5 (2.025.5) |
| Cpre-dose (ng/mL) | 85 (14455) | 498 (<10772) |
| C12h (ng/mL) | 107 (37579) | 77 (3393) |
| Cmax (ng/mL) | 1775 (6856320) | 2760 (3528860) |
| CL/F (L/hr) | 50 (23133) | 54 (16200) |
| Met C12h target | 10/10 | 5/6 |
Table 2: Delivery plasma concentrations, median (range)
| Parameter | n=7 |
| Cord blood raltegravir (ng/mL) | 125 (22939) |
| Maternal delivery plasma raltegravir (ng/mL) | 145 (28626) |
| Cord blood/maternal plasma ratio | 1.20 (0.092.26) |
The investigators concluded: Raltegravir exposure was not consistently altered during third trimester compared to postpartum and historical data and the standard dose appears appropriate during pregnancy.
comment
These data are reassuring.
Ref: Capparelli EV et al. Raltegravir pharmacokinetics during pregnancy. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC),1215 September 2010, Boston. Poster abstract H-1668a.