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The Body PRO Covers: The 13th Conference on Retroviruses and Opportunistic Infections

During the Third Trimester of Pregnancy Lopinavir/Ritonavir Dose Should Be Increased

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.


Abstract: Adequate lopinavir exposure achieved with a higher dose during the third trimester of pregnancy (Poster 710)
Authored by: M Mirochnick, A Stek, E Capparelli, B Best, D Holland, J Connor, S Burchett, C Hu, E Smith, J Read, and the PACTG 1026s Protocol Team

Affiliations: Boston Univ Sch of Publ Hlth, MA, US; David Geffen Sch of Med, Univ of California, Los Angeles Med Ctr, US; Univ of California, San Diego, US; Children's Hosp, Boston, MA, US; Harvard Sch of Publ Hlth, Boston, MA, US; NIAID, NIH, DHHS, Bethesda, MD, US; Natl Inst Child Hlth and Devt, NIH, DHHS, Bethesda, MD, US
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It is a part of the publication The 13th Conference on Retroviruses and Opportunistic Infections.

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