Letter to the Editor: Comparison of Lopinavir Level Between the Two Formulations (Soft-Gel Capsule and Tablet) in HIV-Infected Pregnant Women

Khuong-Josses, Marie-Aude; Azerad, David; Boussairi, A.; Ekoukou, Dieudonné

doi:10.1310/hct0804-254

Cited by 12 publications

(18 citation statements)

References 2 publications

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“…The weights of the participants from these studies were similar to the weights of the participants of our study. The C min and C pd values of the LPV/r standard-dose arm were also similar to those reported in two therapeutic drug monitoring (TDM) trials conducted with pregnant women using this LPV/r dose (18,21) (Table 6). However, the average body weight of those participants was higher than the mean weights of our participants and those from the previously cited studies.…”

Section: Discussionsupporting

confidence: 76%

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Randomized Clinical Trial Comparing the Pharmacokinetics of Standard- and Increased-Dosage Lopinavir-Ritonavir Coformulation Tablets in HIV-Positive Pregnant Women

Santini-Oliveira

Estrela

Veloso

et al. 2014

Antimicrob Agents Chemother

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A lopinavir-ritonavir (LPV/r)-based regimen is recommended during pregnancy to reduce the risk of HIV mother-to-child transmission, but the appropriate dose is controversial. We compared the pharmacokinetics of standard and increased LPV/r doses during pregnancy. This randomized, open-label prospective study enrolled 60 pregnant women between gestational weeks 14 and 30. The participants received either the standard dose (400/100 mg twice a day [BID]) or increased dose (600/150 mg BID) of LPV/r tablets during pregnancy and the standard dose for 6 weeks after childbirth. Pharmacokinetics analysis was performed using a high-performance liquid chromatography-tandem mass spectrometry method. Adherent participants who received the standard dose presented minimum LPV concentrations of 4.4, 4.3, and 6.1 g/ml in the second and third trimesters and postpartum, respectively. The increased-dose group exhibited values of 7.9, 6.9, and 9.2 g/ml at the same three time points. Although LPV exposure was significantly higher in the increased-dose group, the standard dose produced therapeutic levels of LPV against wild-type virus in all adherent participants, except one patient in the third trimester; 50%, 37.5%, and 25%, and 0%, 15%, and 0% of the participants in the standard-and increased-dose groups failed to achieve therapeutic levels against resistant viruses during the second and third trimesters and after childbirth, respectively. After 12 weeks of treatment and after childbirth, all adherent participants achieved undetectable HIV viral loads, and their babies (49/54) were uninfected. No serious drug-related adverse events were observed. We conclude that the standard dose is appropriate for use during pregnancy and that an increased dose may be necessary for women harboring resistant HIV. (This study has been registered at ClinicalTrials.gov under registration no. NCT00605098.)

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Section: Discussionsupporting

confidence: 76%

“…The use of lopinavir coformulated with ritonavir (LPV/r) during pregnancy is recommended in the majority of HIV treatment guidelines (14)(15)(16)(17), even though previous studies have been insufficient to determine the optimal LPV dose during pregnancy (18)(19)(20)(21)(22)(23)(24).…”

mentioning

confidence: 99%

Randomized Clinical Trial Comparing the Pharmacokinetics of Standard- and Increased-Dosage Lopinavir-Ritonavir Coformulation Tablets in HIV-Positive Pregnant Women

Santini-Oliveira

Estrela

Veloso

et al. 2014

Antimicrob Agents Chemother

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“…Previous studies had found no significant difference in LPV trough concentrations between pregnant patients receiving standard doses of the SGC and patients receiving the tablet formulations (17). Equally, we observed equivalent LPV trough concentrations in both cohorts; however, total LPV exposure and maximum concentrations were nonsignificantly higher in patients taking the tablet (cohort 2; n ϭ 11) than those receiving the SGC (cohort 1; n ϭ 6).…”

Section: Discussionsupporting

confidence: 40%

“…In previous cohorts, rates of detectable viral loads at delivery ranged from 6 to 16%; however, most present only isolated cases of detectable viremia or virologic failure specifically associated with subtherapeutic LPV concentrations during pregnancy (17,22,34); in certain cases, these may have been due to poor treatment compliance (20). However, Peytavin et al found in a large patient cohort (n ϭ 101) that LPV trough concentrations in the second and third trimesters were statistically correlated with pVL at delivery (29).…”

Section: Discussionmentioning

confidence: 94%

“…Lambert et al observed significantly reduced LPV concentrations in the second/third trimester; however, the majority of women did achieve concentrations above 1,000 ng/ml; exceptions were in cases where poor treatment adherence was suspected (20). Other studies, however, have reported no pregnancy-associated changes in LPV tablet pharmacokinetics (13,17). The improved oral bioavailability and reduced intersubject variability of the tablet compared with the SGC (18) could indeed compensate for reduced LPV exposure during the later stages of pregnancy.…”

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confidence: 98%

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Improved Oral Bioavailability of Lopinavir in Melt-Extruded Tablet Formulation Reduces Impact of Third Trimester on Lopinavir Plasma Concentrations

Else

Douglas

Dickinson

et al. 2012

Antimicrob Agents Chemother

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Lopinavir exposure was reduced during the third trimester in pregnant women receiving standard dosing of the soft-gel capsule (SGC; 400/100 mg twice daily [b.i.d.]). Pharmacokinetic data on the lopinavir tablet in pregnancy are limited. On the basis of the tablet's improved bioavailability, standard dosing (400/100 mg b.i.d.) may provide adequate lopinavir exposure in pregnancy without a need for dose adjustment. Here we compared the total and unbound lopinavir pharmacokinetics throughout pregnancy in the second and third trimesters in HIV-infected women receiving standard dosing of the lopinavir SGC or tablet. Postpartum sampling was also performed in patients continuing therapy postdelivery. Blood samples were collected at 0 to 12 h postdosing, and lopinavir concentrations were determined by high-pressure liquid chromatography-tandem mass spectrometry. Nineteen patients were included: 8 received the SGC (cohort 1) and 11 received the tablet (cohort 2). Total lopinavir exposures in the third trimester were lower than those in the second trimester (35 and 28% for cohorts 1 and 2, respectively) and postpartum (35% for cohort 2). In the third trimester, the area under the concentration-time curve (AUC) from 0 to 12 h (AUC 0 -12 ) and maximum concentration were ϳ15% and 25% higher, respectively, for the lopinavir tablet than the SGC. One SGC patient had lopinavir concentrations of <1,000 ng/ml; all patients on the tablet had concentrations of >1,000 ng/ml. In cohort 2, the percentage of the AUC that was unbound was higher (nonsignificantly) in the second (1.28%) and third (1.18%) trimesters than postpartum (1.01%). Seventeen of 19 patients had an undetectable viral load at delivery. There were no HIV transmissions. Although lopinavir (tablet) exposures were reduced during the third trimester, the higher total and unbound concentrations achieved in women receiving the tablet than in women receiving the SGC suggest that the tablet's improved oral bioavailability may partly compensate for the reduction in lopinavir exposure during the later stages of pregnancy.A ntiretroviral therapies (ARTs), with the exception of zidovudine, are unlicensed for use in pregnancy. However, they are widely used, in accordance with national and international guidelines, both for maternal treatment and for the prevention of HIV mother-to-child transmission (MTCT). Multiple physiological changes which can impact the pharmacokinetics (PKs) of these agents occur during pregnancy; therefore, studies in pregnancy are required to ensure appropriate dosing and avoid unnecessary toxicity or treatment failure. Protease inhibitors (PIs) are widely used during pregnancy for both treatment and prevention of MTCT due to their efficacy, lack of CD4 count-dependent toxicity, and short half-lives (t 1/2 s). However, plasma concentrations of certain protease inhibitors have repeatedly been shown to be significantly reduced during the third trimester, with some concerns over efficacy (37).Lopinavir (LPV)-ritonavir (RTV), or LPV/r, is used during pregnancy,...

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Pharmacokinetic Enhancement of HIV Antiretroviral Therapy During Pregnancy

Salama

Eke

Best

et al. 2020

The Journal of Clinical Pharma

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Pharmacokinetic boosting of antiretroviral (ARV) therapies with either ritonavir or cobicistat is used to achieve target drug exposure, lower pill burden, and provide simplified dosing schedules. Several ARVs require boosting, including the integrase inhibitor elvitegravir as well as protease inhibitors such as darunavir, atazanavir, and lopinavir. The use of boosted regimens in pregnant women living with HIV has been studied for a variety of ARVs; however, a recent recommendation by the US Food and Drug Administration advised against cobicistat-boosted regimens in pregnancy due to substantially lower drug exposures observed in clinical pharmacokinetic studies. The objectives of this article are to review pharmacokinetic enhancement of ARVs with ritonavir and cobicistat during pregnancy and postpartum, describe clinical implications, and provide recommendations for future research.

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Letter to the Editor: Comparison of Lopinavir Level Between the Two Formulations (Soft-Gel Capsule and Tablet) in HIV-Infected Pregnant Women

Cited by 12 publications

References 2 publications

Randomized Clinical Trial Comparing the Pharmacokinetics of Standard- and Increased-Dosage Lopinavir-Ritonavir Coformulation Tablets in HIV-Positive Pregnant Women

Randomized Clinical Trial Comparing the Pharmacokinetics of Standard- and Increased-Dosage Lopinavir-Ritonavir Coformulation Tablets in HIV-Positive Pregnant Women

Improved Oral Bioavailability of Lopinavir in Melt-Extruded Tablet Formulation Reduces Impact of Third Trimester on Lopinavir Plasma Concentrations

Pharmacokinetic Enhancement of HIV Antiretroviral Therapy During Pregnancy

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