HTB South

Etravirine pregnancy data from five cases: no dose adjustment required

Polly Clayden, HIV i-Base

A pharmacokinetic (PK) and safety study of etravirine (ETR) was conducted in five pregnant women receiving this next generation NNRTI through compassionate use during the clinical development programme.

PK assessments were performed in the third trimester and/or time of delivery. Samples were collected 1, 3, 6 and 12 hours post dose. Cord blood samples were obtained where possible. Plasma concentrations were determined using high performance LC-MS/MS (LLOQ 2ng/mL).

A non-compartmental model was used for the PK analysis and compared with population PK data from earlier trials. The investigators noted that in these trials (DUET-1 and DUET-2) PK parameters did not differ significantly between men and women.

In this study three women received ETR throughout pregnancy and two only in the third trimester.

The investigators reported comparable values in all five women to historical controls. See Table 1.

Three of the women had caesarean sections (one preterm due to twins) and the remainder vaginal deliveries.

The babies were all healthy. One was born with a polyotia but was otherwise normal. No other abnormalities were reported.

The investigators concluded that ETR PK in five pregnant women is comparable to that in non-pregnant adults, which suggests that no dose adjustment is needed. In this small study ETR did not have an effect on foetal toxicity.

ETR in pregnant women will be evaluated further in an ongoing trial investigating PK parameters of darunavir/r and ETR during the second and third trimesters and up to 12 weeks postpartum. [2]

Table 1: PK parameters of ETR in third trimester

Case Tmax (h) Cmax (ng/mL) AUC12h (ng.h/mL) C0h (ng/mL)
1 3 896 4,277* 387
2 6 1,210 6,448* 521
3 3 474 4,788 149
4 3 1150 8,870 898
5 3 445 3,041 434
Mean 835 5,485 478
SD 363 2,253 272
DUET population PK n=575
Mean 5,506 393
SD 4,710 391

AUC=Area under the curve; C=concentration; T=time

* AUC 6h

comment

The importance of conducting these studies and reporting even no effect must be stressed as guidance in this area is vague for many antiretrovirals.

References:

  1. Izurieta P et al. Safety and pharmacokinetics of etravirine in pregnant HIV-infected women. 12th EACS. Cologne. 11-14 November 2009. Abstract PE4.1/6.
  2. A study to assess the pharmacokinetics (blood levels) of TMC114 (darunavir) taken with TMC114r (ritonavir), and TMC125 (etravirine) in HIV-1 infected pregnant women
    http://clinicaltrials.gov/ct2/show/NCT00855335

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