Lopinavir/ritonavir treatment increases the placental transfer of bupivacaine enantiomers in human immunodeficiency virus‐infected pregnant women
Aims The present study evaluated the placental transfer and amniotic fluid distribution of bupivacaine enantiomers in health pregnant women and in human immunodeficiency virus (HIV)‐infected pregnant women receiving epidural anaesthesia for caesarean section. Methods Twelve HIV‐infected pregnant wom...
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| Veröffentlicht in: | British journal of clinical pharmacology 2018-10, Vol.84 (10), p.2415-2421 |
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| creator | Ribeiro, Rodrigo Metzker Pereira Moreira, Fernanda de Lima Moisés, Elaine Christine Dantas Cavalli, Ricardo Carvalho Quintana, Silvana Maria Lanchote, Vera Lucia Duarte, Geraldo |
| description | Aims
The present study evaluated the placental transfer and amniotic fluid distribution of bupivacaine enantiomers in health pregnant women and in human immunodeficiency virus (HIV)‐infected pregnant women receiving epidural anaesthesia for caesarean section.
Methods
Twelve HIV‐infected pregnant women (HIV group) were treated long‐term (at least 8 weeks) with lopinavir/ritonavir (400/100 mg twice daily), and 12 healthy pregnant women (Control group) who submitted to epidural anaesthesia with racemic bupivacaine (75 mg) during caesarean section were investigated. At delivery, samples of maternal and fetal blood and amniotic fluid were collected (10–20 min after drug administration).
Results
The placental transfer ratio of bupivacaine enantiomers was significantly higher among the pregnant women from the HIV group when compared with those from the Control group (Mann–Whitney test, P ≤ 0.05). Placental transfer ratios (median and 25th ‐ 75th percentiles) for (+)‐(R)‐bupivacaine were 0.58 (0.38–0.82) in the HIV group vs. 0.25 (0.18–0.33) in the Control group, and for (–)‐(S)‐bupivacaine, they were 0.54 (0.34–0.69) in the HIV group vs. 0.25 (0.19–0.29) in the Control group. The transplacental distribution of bupivacaine was stereoselective only in the HIV group. The umbilical artery/umbilical vein ratio and amniotic fluid/maternal vein ratio were low and nonstereoselective, and no statistically significant differences were observed between the groups.
Conclusions
This study supports that the placental transfer of both bupivacaine enantiomers was 100% higher in HIV‐pregnant women treated with lopinavir/ritonavir when compared with that in healthy pregnant women receiving epidural anaesthesia for caesarean section. |
| doi_str_mv | 10.1111/bcp.13700 |
| format | Article |
| fullrecord | <record><control><sourceid>wiley_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6138485</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>BCP13700</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4410-fbf752873f95c5e5b60b7a867506a4edc620069177b7deee7de6a9c32cb00a8e3</originalsourceid><addsrcrecordid>eNp1kcFO3DAQhq0KVBbaQ18A-dpDdu1kbSeXSu2KAtJKcKBna-Id7xolTmQni_bGIyD1DfskGLYgOODDeDT-_n9k_YR842zK05nVpp_yQjH2iUx4IUWW81wckAkrmMxELvgROY7xljFecCk-k6O8qkSlqnJC_i673nnYujALbuieOzoEhKFFP1DnTeojRjpskPYNmDSFJhHgo8VAO0vrsXdbMOA8UvTgB9e1GGLS0s3YgqeubUffrdA649CbHU07xvjv_sF5i2bAFe0Drp-U9C5J_RdyaKGJ-PX_fUL-_D67WVxky6vzy8XPZWbmc84yW1sl8lIVthJGoKglqxWUUgkmYY4rI3PGZMWVqtUKEVORUJkiNzVjUGJxQn7sffuxbhOfvhag0X1wLYSd7sDp9y_ebfS622rJi3JeimTwfW9gQhdjQPuq5Uw_JaNTMvo5mcSevl32Sr5EkYDZHrhzDe4-dtK_Ftd7y0cUSJ_z</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Lopinavir/ritonavir treatment increases the placental transfer of bupivacaine enantiomers in human immunodeficiency virus‐infected pregnant women</title><source>Wiley Free Content</source><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Wiley Online Library All Journals</source><creator>Ribeiro, Rodrigo Metzker Pereira ; Moreira, Fernanda de Lima ; Moisés, Elaine Christine Dantas ; Cavalli, Ricardo Carvalho ; Quintana, Silvana Maria ; Lanchote, Vera Lucia ; Duarte, Geraldo</creator><creatorcontrib>Ribeiro, Rodrigo Metzker Pereira ; Moreira, Fernanda de Lima ; Moisés, Elaine Christine Dantas ; Cavalli, Ricardo Carvalho ; Quintana, Silvana Maria ; Lanchote, Vera Lucia ; Duarte, Geraldo</creatorcontrib><description>Aims
The present study evaluated the placental transfer and amniotic fluid distribution of bupivacaine enantiomers in health pregnant women and in human immunodeficiency virus (HIV)‐infected pregnant women receiving epidural anaesthesia for caesarean section.
Methods
Twelve HIV‐infected pregnant women (HIV group) were treated long‐term (at least 8 weeks) with lopinavir/ritonavir (400/100 mg twice daily), and 12 healthy pregnant women (Control group) who submitted to epidural anaesthesia with racemic bupivacaine (75 mg) during caesarean section were investigated. At delivery, samples of maternal and fetal blood and amniotic fluid were collected (10–20 min after drug administration).
Results
The placental transfer ratio of bupivacaine enantiomers was significantly higher among the pregnant women from the HIV group when compared with those from the Control group (Mann–Whitney test, P ≤ 0.05). Placental transfer ratios (median and 25th ‐ 75th percentiles) for (+)‐(R)‐bupivacaine were 0.58 (0.38–0.82) in the HIV group vs. 0.25 (0.18–0.33) in the Control group, and for (–)‐(S)‐bupivacaine, they were 0.54 (0.34–0.69) in the HIV group vs. 0.25 (0.19–0.29) in the Control group. The transplacental distribution of bupivacaine was stereoselective only in the HIV group. The umbilical artery/umbilical vein ratio and amniotic fluid/maternal vein ratio were low and nonstereoselective, and no statistically significant differences were observed between the groups.
Conclusions
This study supports that the placental transfer of both bupivacaine enantiomers was 100% higher in HIV‐pregnant women treated with lopinavir/ritonavir when compared with that in healthy pregnant women receiving epidural anaesthesia for caesarean section.</description><identifier>ISSN: 0306-5251</identifier><identifier>EISSN: 1365-2125</identifier><identifier>DOI: 10.1111/bcp.13700</identifier><identifier>PMID: 29959798</identifier><language>eng</language><publisher>England: John Wiley and Sons Inc</publisher><subject>Adult ; amniotic fluid ; Amniotic Fluid - chemistry ; Anesthesia, Epidural - adverse effects ; Anesthesia, Epidural - methods ; Anesthesia, Obstetrical - adverse effects ; Anesthesia, Obstetrical - methods ; Anesthetics, Local - administration & dosage ; Anesthetics, Local - pharmacokinetics ; antiretroviral ; bupivacaine ; Bupivacaine - administration & dosage ; Bupivacaine - pharmacokinetics ; Case-Control Studies ; Cesarean Section - adverse effects ; cord blood ; Drug Combinations ; enantiomers ; Female ; Fetal Blood - chemistry ; HIV Infections - drug therapy ; HIV Protease Inhibitors - adverse effects ; human immunodeficiency virus ; Humans ; Lopinavir - adverse effects ; Maternal-Fetal Exchange - drug effects ; Original ; Permeability ; Placenta - drug effects ; Placenta - metabolism ; Pregnancy ; Pregnancy Complications, Infectious - drug therapy ; Ritonavir - adverse effects</subject><ispartof>British journal of clinical pharmacology, 2018-10, Vol.84 (10), p.2415-2421</ispartof><rights>2018 The British Pharmacological Society</rights><rights>2018 The British Pharmacological Society.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4410-fbf752873f95c5e5b60b7a867506a4edc620069177b7deee7de6a9c32cb00a8e3</citedby><cites>FETCH-LOGICAL-c4410-fbf752873f95c5e5b60b7a867506a4edc620069177b7deee7de6a9c32cb00a8e3</cites><orcidid>0000-0002-0074-4953 ; 0000-0002-1689-6142 ; 0000-0001-5010-4914 ; 0000-0001-9099-4544 ; 0000-0001-7699-2665 ; 0000-0002-9311-786X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fbcp.13700$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fbcp.13700$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29959798$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ribeiro, Rodrigo Metzker Pereira</creatorcontrib><creatorcontrib>Moreira, Fernanda de Lima</creatorcontrib><creatorcontrib>Moisés, Elaine Christine Dantas</creatorcontrib><creatorcontrib>Cavalli, Ricardo Carvalho</creatorcontrib><creatorcontrib>Quintana, Silvana Maria</creatorcontrib><creatorcontrib>Lanchote, Vera Lucia</creatorcontrib><creatorcontrib>Duarte, Geraldo</creatorcontrib><title>Lopinavir/ritonavir treatment increases the placental transfer of bupivacaine enantiomers in human immunodeficiency virus‐infected pregnant women</title><title>British journal of clinical pharmacology</title><addtitle>Br J Clin Pharmacol</addtitle><description>Aims
The present study evaluated the placental transfer and amniotic fluid distribution of bupivacaine enantiomers in health pregnant women and in human immunodeficiency virus (HIV)‐infected pregnant women receiving epidural anaesthesia for caesarean section.
Methods
Twelve HIV‐infected pregnant women (HIV group) were treated long‐term (at least 8 weeks) with lopinavir/ritonavir (400/100 mg twice daily), and 12 healthy pregnant women (Control group) who submitted to epidural anaesthesia with racemic bupivacaine (75 mg) during caesarean section were investigated. At delivery, samples of maternal and fetal blood and amniotic fluid were collected (10–20 min after drug administration).
Results
The placental transfer ratio of bupivacaine enantiomers was significantly higher among the pregnant women from the HIV group when compared with those from the Control group (Mann–Whitney test, P ≤ 0.05). Placental transfer ratios (median and 25th ‐ 75th percentiles) for (+)‐(R)‐bupivacaine were 0.58 (0.38–0.82) in the HIV group vs. 0.25 (0.18–0.33) in the Control group, and for (–)‐(S)‐bupivacaine, they were 0.54 (0.34–0.69) in the HIV group vs. 0.25 (0.19–0.29) in the Control group. The transplacental distribution of bupivacaine was stereoselective only in the HIV group. The umbilical artery/umbilical vein ratio and amniotic fluid/maternal vein ratio were low and nonstereoselective, and no statistically significant differences were observed between the groups.
Conclusions
This study supports that the placental transfer of both bupivacaine enantiomers was 100% higher in HIV‐pregnant women treated with lopinavir/ritonavir when compared with that in healthy pregnant women receiving epidural anaesthesia for caesarean section.</description><subject>Adult</subject><subject>amniotic fluid</subject><subject>Amniotic Fluid - chemistry</subject><subject>Anesthesia, Epidural - adverse effects</subject><subject>Anesthesia, Epidural - methods</subject><subject>Anesthesia, Obstetrical - adverse effects</subject><subject>Anesthesia, Obstetrical - methods</subject><subject>Anesthetics, Local - administration & dosage</subject><subject>Anesthetics, Local - pharmacokinetics</subject><subject>antiretroviral</subject><subject>bupivacaine</subject><subject>Bupivacaine - administration & dosage</subject><subject>Bupivacaine - pharmacokinetics</subject><subject>Case-Control Studies</subject><subject>Cesarean Section - adverse effects</subject><subject>cord blood</subject><subject>Drug Combinations</subject><subject>enantiomers</subject><subject>Female</subject><subject>Fetal Blood - chemistry</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Protease Inhibitors - adverse effects</subject><subject>human immunodeficiency virus</subject><subject>Humans</subject><subject>Lopinavir - adverse effects</subject><subject>Maternal-Fetal Exchange - drug effects</subject><subject>Original</subject><subject>Permeability</subject><subject>Placenta - drug effects</subject><subject>Placenta - metabolism</subject><subject>Pregnancy</subject><subject>Pregnancy Complications, Infectious - drug therapy</subject><subject>Ritonavir - adverse effects</subject><issn>0306-5251</issn><issn>1365-2125</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kcFO3DAQhq0KVBbaQ18A-dpDdu1kbSeXSu2KAtJKcKBna-Id7xolTmQni_bGIyD1DfskGLYgOODDeDT-_n9k_YR842zK05nVpp_yQjH2iUx4IUWW81wckAkrmMxELvgROY7xljFecCk-k6O8qkSlqnJC_i673nnYujALbuieOzoEhKFFP1DnTeojRjpskPYNmDSFJhHgo8VAO0vrsXdbMOA8UvTgB9e1GGLS0s3YgqeubUffrdA649CbHU07xvjv_sF5i2bAFe0Drp-U9C5J_RdyaKGJ-PX_fUL-_D67WVxky6vzy8XPZWbmc84yW1sl8lIVthJGoKglqxWUUgkmYY4rI3PGZMWVqtUKEVORUJkiNzVjUGJxQn7sffuxbhOfvhag0X1wLYSd7sDp9y_ebfS622rJi3JeimTwfW9gQhdjQPuq5Uw_JaNTMvo5mcSevl32Sr5EkYDZHrhzDe4-dtK_Ftd7y0cUSJ_z</recordid><startdate>201810</startdate><enddate>201810</enddate><creator>Ribeiro, Rodrigo Metzker Pereira</creator><creator>Moreira, Fernanda de Lima</creator><creator>Moisés, Elaine Christine Dantas</creator><creator>Cavalli, Ricardo Carvalho</creator><creator>Quintana, Silvana Maria</creator><creator>Lanchote, Vera Lucia</creator><creator>Duarte, Geraldo</creator><general>John Wiley and Sons Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0074-4953</orcidid><orcidid>https://orcid.org/0000-0002-1689-6142</orcidid><orcidid>https://orcid.org/0000-0001-5010-4914</orcidid><orcidid>https://orcid.org/0000-0001-9099-4544</orcidid><orcidid>https://orcid.org/0000-0001-7699-2665</orcidid><orcidid>https://orcid.org/0000-0002-9311-786X</orcidid></search><sort><creationdate>201810</creationdate><title>Lopinavir/ritonavir treatment increases the placental transfer of bupivacaine enantiomers in human immunodeficiency virus‐infected pregnant women</title><author>Ribeiro, Rodrigo Metzker Pereira ; Moreira, Fernanda de Lima ; Moisés, Elaine Christine Dantas ; Cavalli, Ricardo Carvalho ; Quintana, Silvana Maria ; Lanchote, Vera Lucia ; Duarte, Geraldo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4410-fbf752873f95c5e5b60b7a867506a4edc620069177b7deee7de6a9c32cb00a8e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>amniotic fluid</topic><topic>Amniotic Fluid - chemistry</topic><topic>Anesthesia, Epidural - adverse effects</topic><topic>Anesthesia, Epidural - methods</topic><topic>Anesthesia, Obstetrical - adverse effects</topic><topic>Anesthesia, Obstetrical - methods</topic><topic>Anesthetics, Local - administration & dosage</topic><topic>Anesthetics, Local - pharmacokinetics</topic><topic>antiretroviral</topic><topic>bupivacaine</topic><topic>Bupivacaine - administration & dosage</topic><topic>Bupivacaine - pharmacokinetics</topic><topic>Case-Control Studies</topic><topic>Cesarean Section - adverse effects</topic><topic>cord blood</topic><topic>Drug Combinations</topic><topic>enantiomers</topic><topic>Female</topic><topic>Fetal Blood - chemistry</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Protease Inhibitors - adverse effects</topic><topic>human immunodeficiency virus</topic><topic>Humans</topic><topic>Lopinavir - adverse effects</topic><topic>Maternal-Fetal Exchange - drug effects</topic><topic>Original</topic><topic>Permeability</topic><topic>Placenta - drug effects</topic><topic>Placenta - metabolism</topic><topic>Pregnancy</topic><topic>Pregnancy Complications, Infectious - drug therapy</topic><topic>Ritonavir - adverse effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ribeiro, Rodrigo Metzker Pereira</creatorcontrib><creatorcontrib>Moreira, Fernanda de Lima</creatorcontrib><creatorcontrib>Moisés, Elaine Christine Dantas</creatorcontrib><creatorcontrib>Cavalli, Ricardo Carvalho</creatorcontrib><creatorcontrib>Quintana, Silvana Maria</creatorcontrib><creatorcontrib>Lanchote, Vera Lucia</creatorcontrib><creatorcontrib>Duarte, Geraldo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ribeiro, Rodrigo Metzker Pereira</au><au>Moreira, Fernanda de Lima</au><au>Moisés, Elaine Christine Dantas</au><au>Cavalli, Ricardo Carvalho</au><au>Quintana, Silvana Maria</au><au>Lanchote, Vera Lucia</au><au>Duarte, Geraldo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lopinavir/ritonavir treatment increases the placental transfer of bupivacaine enantiomers in human immunodeficiency virus‐infected pregnant women</atitle><jtitle>British journal of clinical pharmacology</jtitle><addtitle>Br J Clin Pharmacol</addtitle><date>2018-10</date><risdate>2018</risdate><volume>84</volume><issue>10</issue><spage>2415</spage><epage>2421</epage><pages>2415-2421</pages><issn>0306-5251</issn><eissn>1365-2125</eissn><abstract>Aims
The present study evaluated the placental transfer and amniotic fluid distribution of bupivacaine enantiomers in health pregnant women and in human immunodeficiency virus (HIV)‐infected pregnant women receiving epidural anaesthesia for caesarean section.
Methods
Twelve HIV‐infected pregnant women (HIV group) were treated long‐term (at least 8 weeks) with lopinavir/ritonavir (400/100 mg twice daily), and 12 healthy pregnant women (Control group) who submitted to epidural anaesthesia with racemic bupivacaine (75 mg) during caesarean section were investigated. At delivery, samples of maternal and fetal blood and amniotic fluid were collected (10–20 min after drug administration).
Results
The placental transfer ratio of bupivacaine enantiomers was significantly higher among the pregnant women from the HIV group when compared with those from the Control group (Mann–Whitney test, P ≤ 0.05). Placental transfer ratios (median and 25th ‐ 75th percentiles) for (+)‐(R)‐bupivacaine were 0.58 (0.38–0.82) in the HIV group vs. 0.25 (0.18–0.33) in the Control group, and for (–)‐(S)‐bupivacaine, they were 0.54 (0.34–0.69) in the HIV group vs. 0.25 (0.19–0.29) in the Control group. The transplacental distribution of bupivacaine was stereoselective only in the HIV group. The umbilical artery/umbilical vein ratio and amniotic fluid/maternal vein ratio were low and nonstereoselective, and no statistically significant differences were observed between the groups.
Conclusions
This study supports that the placental transfer of both bupivacaine enantiomers was 100% higher in HIV‐pregnant women treated with lopinavir/ritonavir when compared with that in healthy pregnant women receiving epidural anaesthesia for caesarean section.</abstract><cop>England</cop><pub>John Wiley and Sons Inc</pub><pmid>29959798</pmid><doi>10.1111/bcp.13700</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-0074-4953</orcidid><orcidid>https://orcid.org/0000-0002-1689-6142</orcidid><orcidid>https://orcid.org/0000-0001-5010-4914</orcidid><orcidid>https://orcid.org/0000-0001-9099-4544</orcidid><orcidid>https://orcid.org/0000-0001-7699-2665</orcidid><orcidid>https://orcid.org/0000-0002-9311-786X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult amniotic fluid Amniotic Fluid - chemistry Anesthesia, Epidural - adverse effects Anesthesia, Epidural - methods Anesthesia, Obstetrical - adverse effects Anesthesia, Obstetrical - methods Anesthetics, Local - administration & dosage Anesthetics, Local - pharmacokinetics antiretroviral bupivacaine Bupivacaine - administration & dosage Bupivacaine - pharmacokinetics Case-Control Studies Cesarean Section - adverse effects cord blood Drug Combinations enantiomers Female Fetal Blood - chemistry HIV Infections - drug therapy HIV Protease Inhibitors - adverse effects human immunodeficiency virus Humans Lopinavir - adverse effects Maternal-Fetal Exchange - drug effects Original Permeability Placenta - drug effects Placenta - metabolism Pregnancy Pregnancy Complications, Infectious - drug therapy Ritonavir - adverse effects |
| title | Lopinavir/ritonavir treatment increases the placental transfer of bupivacaine enantiomers in human immunodeficiency virus‐infected pregnant women |
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