Therapeutic drug monitoring of lopinavir/ritonavir in pregnancy.

Hdl Handle:
http://hdl.handle.net/10147/144282
Title:
Therapeutic drug monitoring of lopinavir/ritonavir in pregnancy.
Authors:
Lambert, J S; Else, L J; Jackson, V; Breiden, J; Gibbons, S; Dickinson, L; Back, D J; Brennan, M; Connor, E O; Boyle, N; Fleming, C; Coulter-Smith, S; Khoo, S H
Affiliation:
The Rotunda Hospital, Dublin, Ireland.
Citation:
Therapeutic drug monitoring of lopinavir/ritonavir in pregnancy. 2011, 12 (3):166-73 HIV Med.
Journal:
HIV medicine
Issue Date:
Mar-2011
URI:
http://hdl.handle.net/10147/144282
DOI:
10.1111/j.1468-1293.2010.00865.x
PubMed ID:
20726906
Additional Links:
http://onlinelibrary.wiley.com/doi/10.1111/j.1468-1293.2010.00865.x/abstract;jsessionid=405F26BBACE83E92C33F86A8726513BF.d01t02?systemMessage=Wiley+Online+Library+will+be+disrupted+8+Oct+from+10-14+BST+for+monthly+maintenance
Abstract:
The aim of the study was to determine total and unbound lopinavir (LPV) plasma concentrations in HIV-infected pregnant women receiving lopinavir/ritonavir (LPV/r tablet) undergoing therapeutic drug monitoring (TDM) during pregnancy and postpartum.; Women were enrolled in the study who were receiving the LPV/r tablet as part of their routine prenatal care. Demographic and clinical data were collected and LPV plasma (total) and ultrafiltrate (unbound) concentrations were determined in the first, second and third trimesters using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Postpartum sampling was performed where applicable. Antepartum and postpartum trough concentrations (C(trough) ) were compared independently [using analysis of variance (anova)] and on a longitudinal basis (using a paired t-test).; Forty-six women were enrolled in the study (38 Black African). Forty women initiated LPV/r treatment in pregnancy. Median (range) gestation at initiation was 25 (15-36) weeks and median (range) baseline CD4 count and viral load were 346 (14-836) cells/μL and 8724 (<50-267408) HIV-1 RNA copies/mL, respectively. Forty women (87%) had LPV concentrations above the accepted minimum effective concentration for wild-type virus (MEC; 1000 ng/mL). Geometric mean (95% confidence interval [CI]) total LPV concentrations in the first/second [3525 (2823-4227) ng/mL; n=16] and third [3346 (2813-3880) ng/mL; n=43] trimesters were significantly lower relative to postpartum [5136 (3693-6579) ng/mL; n=12] (P=0.006). In a paired analysis (n=12), LPV concentrations were reduced in the third trimester [3657 (2851-4463) ng/mL] vs. postpartum (P=0.021). No significant differences were observed in the LPV fraction unbound (fu%). Conclusions The above target concentrations achieved in the majority of women and similarities in the fu% suggest standard dosing of the LPV/r tablet is appropriate during pregnancy. However, reduced LPV concentrations in the second/third trimesters and potentially compromised adherence highlight the need for TDM-guided dose adjustment in certain cases.
Item Type:
Article
Language:
en
Description:
OBJECTIVES: The aim of the study was to determine total and unbound lopinavir (LPV) plasma concentrations in HIV-infected pregnant women receiving lopinavir/ritonavir (LPV/r tablet) undergoing therapeutic drug monitoring (TDM) during pregnancy and postpartum. METHODS: Women were enrolled in the study who were receiving the LPV/r tablet as part of their routine prenatal care. Demographic and clinical data were collected and LPV plasma (total) and ultrafiltrate (unbound) concentrations were determined in the first, second and third trimesters using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Postpartum sampling was performed where applicable. Antepartum and postpartum trough concentrations (C(trough) ) were compared independently [using analysis of variance (anova)] and on a longitudinal basis (using a paired t-test). RESULTS: Forty-six women were enrolled in the study (38 Black African). Forty women initiated LPV/r treatment in pregnancy. Median (range) gestation at initiation was 25 (15-36) weeks and median (range) baseline CD4 count and viral load were 346 (14-836) cells/μL and 8724 (<50-267408) HIV-1 RNA copies/mL, respectively. Forty women (87%) had LPV concentrations above the accepted minimum effective concentration for wild-type virus (MEC; 1000 ng/mL). Geometric mean (95% confidence interval [CI]) total LPV concentrations in the first/second [3525 (2823-4227) ng/mL; n=16] and third [3346 (2813-3880) ng/mL; n=43] trimesters were significantly lower relative to postpartum [5136 (3693-6579) ng/mL; n=12] (P=0.006). In a paired analysis (n=12), LPV concentrations were reduced in the third trimester [3657 (2851-4463) ng/mL] vs. postpartum (P=0.021). No significant differences were observed in the LPV fraction unbound (fu%). Conclusions The above target concentrations achieved in the majority of women and similarities in the fu% suggest standard dosing of the LPV/r tablet is appropriate during pregnancy. However, reduced LPV concentrations in the second/third trimesters and potentially compromised adherence highlight the need for TDM-guided dose adjustment in certain cases.
MeSH:
Adult; Anti-HIV Agents; Chromatography, High Pressure Liquid; Drug Monitoring; Female; HIV Infections; HIV-1; Humans; Pregnancy; Pregnancy Complications, Infectious; Pyrimidinones; Ritonavir; Young Adult
ISSN:
1468-1293

Full metadata record

DC FieldValue Language
dc.contributor.authorLambert, J Sen
dc.contributor.authorElse, L Jen
dc.contributor.authorJackson, Ven
dc.contributor.authorBreiden, Jen
dc.contributor.authorGibbons, Sen
dc.contributor.authorDickinson, Len
dc.contributor.authorBack, D Jen
dc.contributor.authorBrennan, Men
dc.contributor.authorConnor, E Oen
dc.contributor.authorBoyle, Nen
dc.contributor.authorFleming, Cen
dc.contributor.authorCoulter-Smith, Sen
dc.contributor.authorKhoo, S Hen
dc.date.accessioned2011-10-07T14:12:01Z-
dc.date.available2011-10-07T14:12:01Z-
dc.date.issued2011-03-
dc.identifier.citationTherapeutic drug monitoring of lopinavir/ritonavir in pregnancy. 2011, 12 (3):166-73 HIV Med.en
dc.identifier.issn1468-1293-
dc.identifier.pmid20726906-
dc.identifier.doi10.1111/j.1468-1293.2010.00865.x-
dc.identifier.urihttp://hdl.handle.net/10147/144282-
dc.descriptionOBJECTIVES: The aim of the study was to determine total and unbound lopinavir (LPV) plasma concentrations in HIV-infected pregnant women receiving lopinavir/ritonavir (LPV/r tablet) undergoing therapeutic drug monitoring (TDM) during pregnancy and postpartum. METHODS: Women were enrolled in the study who were receiving the LPV/r tablet as part of their routine prenatal care. Demographic and clinical data were collected and LPV plasma (total) and ultrafiltrate (unbound) concentrations were determined in the first, second and third trimesters using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Postpartum sampling was performed where applicable. Antepartum and postpartum trough concentrations (C(trough) ) were compared independently [using analysis of variance (anova)] and on a longitudinal basis (using a paired t-test). RESULTS: Forty-six women were enrolled in the study (38 Black African). Forty women initiated LPV/r treatment in pregnancy. Median (range) gestation at initiation was 25 (15-36) weeks and median (range) baseline CD4 count and viral load were 346 (14-836) cells/μL and 8724 (<50-267408) HIV-1 RNA copies/mL, respectively. Forty women (87%) had LPV concentrations above the accepted minimum effective concentration for wild-type virus (MEC; 1000 ng/mL). Geometric mean (95% confidence interval [CI]) total LPV concentrations in the first/second [3525 (2823-4227) ng/mL; n=16] and third [3346 (2813-3880) ng/mL; n=43] trimesters were significantly lower relative to postpartum [5136 (3693-6579) ng/mL; n=12] (P=0.006). In a paired analysis (n=12), LPV concentrations were reduced in the third trimester [3657 (2851-4463) ng/mL] vs. postpartum (P=0.021). No significant differences were observed in the LPV fraction unbound (fu%). Conclusions The above target concentrations achieved in the majority of women and similarities in the fu% suggest standard dosing of the LPV/r tablet is appropriate during pregnancy. However, reduced LPV concentrations in the second/third trimesters and potentially compromised adherence highlight the need for TDM-guided dose adjustment in certain cases.en
dc.description.abstractThe aim of the study was to determine total and unbound lopinavir (LPV) plasma concentrations in HIV-infected pregnant women receiving lopinavir/ritonavir (LPV/r tablet) undergoing therapeutic drug monitoring (TDM) during pregnancy and postpartum.-
dc.description.abstractWomen were enrolled in the study who were receiving the LPV/r tablet as part of their routine prenatal care. Demographic and clinical data were collected and LPV plasma (total) and ultrafiltrate (unbound) concentrations were determined in the first, second and third trimesters using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Postpartum sampling was performed where applicable. Antepartum and postpartum trough concentrations (C(trough) ) were compared independently [using analysis of variance (anova)] and on a longitudinal basis (using a paired t-test).-
dc.description.abstractForty-six women were enrolled in the study (38 Black African). Forty women initiated LPV/r treatment in pregnancy. Median (range) gestation at initiation was 25 (15-36) weeks and median (range) baseline CD4 count and viral load were 346 (14-836) cells/μL and 8724 (<50-267408) HIV-1 RNA copies/mL, respectively. Forty women (87%) had LPV concentrations above the accepted minimum effective concentration for wild-type virus (MEC; 1000 ng/mL). Geometric mean (95% confidence interval [CI]) total LPV concentrations in the first/second [3525 (2823-4227) ng/mL; n=16] and third [3346 (2813-3880) ng/mL; n=43] trimesters were significantly lower relative to postpartum [5136 (3693-6579) ng/mL; n=12] (P=0.006). In a paired analysis (n=12), LPV concentrations were reduced in the third trimester [3657 (2851-4463) ng/mL] vs. postpartum (P=0.021). No significant differences were observed in the LPV fraction unbound (fu%). Conclusions The above target concentrations achieved in the majority of women and similarities in the fu% suggest standard dosing of the LPV/r tablet is appropriate during pregnancy. However, reduced LPV concentrations in the second/third trimesters and potentially compromised adherence highlight the need for TDM-guided dose adjustment in certain cases.-
dc.language.isoenen
dc.relation.urlhttp://onlinelibrary.wiley.com/doi/10.1111/j.1468-1293.2010.00865.x/abstract;jsessionid=405F26BBACE83E92C33F86A8726513BF.d01t02?systemMessage=Wiley+Online+Library+will+be+disrupted+8+Oct+from+10-14+BST+for+monthly+maintenanceen
dc.subject.meshAdult-
dc.subject.meshAnti-HIV Agents-
dc.subject.meshChromatography, High Pressure Liquid-
dc.subject.meshDrug Monitoring-
dc.subject.meshFemale-
dc.subject.meshHIV Infections-
dc.subject.meshHIV-1-
dc.subject.meshHumans-
dc.subject.meshPregnancy-
dc.subject.meshPregnancy Complications, Infectious-
dc.subject.meshPyrimidinones-
dc.subject.meshRitonavir-
dc.subject.meshYoung Adult-
dc.titleTherapeutic drug monitoring of lopinavir/ritonavir in pregnancy.en
dc.typeArticleen
dc.contributor.departmentThe Rotunda Hospital, Dublin, Ireland.en
dc.identifier.journalHIV medicineen
dc.description.provinceLeinster-

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