February 6, 2006
During pregnancy, the pharmacokinetics of many drugs are altered. Due to a higher volume of distribution, many medications have lower plasma levels. For example, a prior study has shown that pregnant women receiving lopinavir/ritonavir (LPV/r, Kaletra) at the standard adult dose of 400 mg/100 mg have reduced lopinavir exposure compared with nonpregnant adults. This study, presented here by M. Mirochnick et al, sought to determine lopinavir exposures using a higher lopinavir/ritonavir dose during the third trimester, specifically 533 mg/133 mg (four caps) twice daily.
Pharmacokinetic data were available for 23 women. The use of higher dose lopinavir/ritonavir achieved target lopinavir concentrations during the third trimester, with significantly higher area under the curve (AUC) and trough (Cmin) levels compared with standard dosing. A small amount of lopinavir was also detected in umbilical cord blood samples. Plasma samples obtained two weeks postpartum yielded concentrations that exceeded target levels. According to the lead study investigator, no HIV transmission to the newborn occurred.
The results of the study confirm that increasing the dose of lopinavir/ritonavir during the third trimester will achieve lopinavir levels comparable to those in nonpregnant patients. Interestingly, a study from London (abstract 709) of 16 pregnant women did not find suboptimal concentrations with standard dosing.
What are the practical implications of these apparently conflicting results? Clinicians should strongly consider increasing the dose of lopinavir/ritonavir during the third trimester, and then quickly resume standard dosing after delivery. In addition, we should watch closely for results of pharmacokinetic studies using the new tablet formulation of lopinavir/ritonavir in this patient population.
|Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.|