Therapeutic drug monitoring of lopinavir/ritonavir in pregnancy.

Hdl Handle:
http://hdl.handle.net/10147/207724
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:
HIV Med. 2011 Mar;12(3):166-73. doi: 10.1111/j.1468-1293.2010.00865.x. Epub 2010 , Aug 18.
Journal:
HIV medicine
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207724
DOI:
10.1111/j.1468-1293.2010.00865.x
PubMed ID:
20726906
Abstract:
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/muL 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.
Language:
eng
MeSH:
Adult; Anti-HIV Agents/*blood/pharmacokinetics/therapeutic use; Chromatography, High Pressure Liquid; Drug Monitoring; Female; HIV Infections/blood/*drug therapy; *HIV-1; Humans; Lopinavir; Pregnancy; Pregnancy Complications, Infectious/blood/*drug therapy; Pyrimidinones/*blood/pharmacokinetics/therapeutic use; Ritonavir/*blood/pharmacokinetics/therapeutic use; Young Adult
ISSN:
1468-1293 (Electronic); 1464-2662 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorLambert, J Sen_GB
dc.contributor.authorElse, L Jen_GB
dc.contributor.authorJackson, Ven_GB
dc.contributor.authorBreiden, Jen_GB
dc.contributor.authorGibbons, Sen_GB
dc.contributor.authorDickinson, Len_GB
dc.contributor.authorBack, D Jen_GB
dc.contributor.authorBrennan, Men_GB
dc.contributor.authorConnor, E Oen_GB
dc.contributor.authorBoyle, Nen_GB
dc.contributor.authorFleming, Cen_GB
dc.contributor.authorCoulter-Smith, Sen_GB
dc.contributor.authorKhoo, S Hen_GB
dc.date.accessioned2012-02-01T10:38:05Z-
dc.date.available2012-02-01T10:38:05Z-
dc.date.issued2012-02-01T10:38:05Z-
dc.identifier.citationHIV Med. 2011 Mar;12(3):166-73. doi: 10.1111/j.1468-1293.2010.00865.x. Epub 2010 , Aug 18.en_GB
dc.identifier.issn1468-1293 (Electronic)en_GB
dc.identifier.issn1464-2662 (Linking)en_GB
dc.identifier.pmid20726906en_GB
dc.identifier.doi10.1111/j.1468-1293.2010.00865.xen_GB
dc.identifier.urihttp://hdl.handle.net/10147/207724-
dc.description.abstractOBJECTIVES: 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/muL 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_GB
dc.language.isoengen_GB
dc.subject.meshAdulten_GB
dc.subject.meshAnti-HIV Agents/*blood/pharmacokinetics/therapeutic useen_GB
dc.subject.meshChromatography, High Pressure Liquiden_GB
dc.subject.meshDrug Monitoringen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshHIV Infections/blood/*drug therapyen_GB
dc.subject.mesh*HIV-1en_GB
dc.subject.meshHumansen_GB
dc.subject.meshLopinaviren_GB
dc.subject.meshPregnancyen_GB
dc.subject.meshPregnancy Complications, Infectious/blood/*drug therapyen_GB
dc.subject.meshPyrimidinones/*blood/pharmacokinetics/therapeutic useen_GB
dc.subject.meshRitonavir/*blood/pharmacokinetics/therapeutic useen_GB
dc.subject.meshYoung Adulten_GB
dc.titleTherapeutic drug monitoring of lopinavir/ritonavir in pregnancy.en_GB
dc.contributor.departmentThe Rotunda Hospital, Dublin, Ireland.en_GB
dc.identifier.journalHIV medicineen_GB
dc.description.provinceLeinster-

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