Suboptimal nevirapine steady-state pharmacokinetics during intrapartum compared with postpartum in HIV-1-seropositive Ugandan women

Mohammed Lamorde, Pauline Byakika-Kibwika, Violet Okaba-Kayom, John P. Flaherty, Marta Boffito, Rhoda Namakula, Mairin Ryan, Clemensia Nakabiito, David J. Back, Saye Khoo, Concepta Merry, Kimberly K. Scarsi

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Abstract

Background: Conflicting data exist regarding the effect of pregnancy on steady-state nevirapine pharmacokinetics (PK), although steady-state nevirapine concentrations during pregnancy have never been characterized in sub-Saharan Africa. Methods: This was a longitudinal intensive PK study in Ugandan pregnant women receiving nevirapine-based antiretroviral therapy. Participants underwent intensive 12-hour PK sampling during the second trimester (T2; n = 4), third trimester (T3; n = 15) and 6 weeks postpartum (PP; n = 15). HIV-1 RNA was performed within 2 weeks of each visit. Nevirapine C12 above 3000 ng/mL was classified as optimal based on the suggested value for therapeutic drug monitoring. Results: The pharmacokinetics of nevirapine were influenced by pregnancy, demonstrated by a 20% reduction in the maximum concentration, minimum concentration (C12), and area under the curve between T3 and PP visits (P = 0.001, P = 0.011 and P = 0.005, respectively). Ten subjects (66.7%) had C12 values <3000 ng/mL during T3. Of these participants, 7 partcipant's C12 concentrations increased to >3000 ng/mL during the PP visit. HIV-1 RNA were <1000 copies per milliliter at T3 and <400 copies per milliliter at PP in all patients. Conclusions: Nevirapine exposure was reduced in Ugandan women during their third trimester compared with the same women PP, however, HIV RNA remained <1000 copies per milliliter. The long-term impact of intermittent suboptimal nevirapine concentrations during pregnancy is unknown.

Original languageEnglish (US)
Pages (from-to)345-350
Number of pages6
JournalJournal of Acquired Immune Deficiency Syndromes
Volume55
Issue number3
DOIs
StatePublished - Nov 1 2010

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Nevirapine
Postpartum Period
HIV-1
Pharmacokinetics
Pregnancy
Third Pregnancy Trimester
RNA
Drug Monitoring
Africa South of the Sahara
Second Pregnancy Trimester
Area Under Curve
Pregnant Women
HIV

Keywords

  • HIV
  • Sub-Saharan Africa
  • antiretroviral agents
  • pharmacokinetics
  • pregnancy

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Suboptimal nevirapine steady-state pharmacokinetics during intrapartum compared with postpartum in HIV-1-seropositive Ugandan women. / Lamorde, Mohammed; Byakika-Kibwika, Pauline; Okaba-Kayom, Violet; Flaherty, John P.; Boffito, Marta; Namakula, Rhoda; Ryan, Mairin; Nakabiito, Clemensia; Back, David J.; Khoo, Saye; Merry, Concepta; Scarsi, Kimberly K.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 55, No. 3, 01.11.2010, p. 345-350.

Research output: Contribution to journalArticle

Lamorde, M, Byakika-Kibwika, P, Okaba-Kayom, V, Flaherty, JP, Boffito, M, Namakula, R, Ryan, M, Nakabiito, C, Back, DJ, Khoo, S, Merry, C & Scarsi, KK 2010, 'Suboptimal nevirapine steady-state pharmacokinetics during intrapartum compared with postpartum in HIV-1-seropositive Ugandan women', Journal of Acquired Immune Deficiency Syndromes, vol. 55, no. 3, pp. 345-350. https://doi.org/10.1097/QAI.0b013e3181e9871b
Lamorde, Mohammed ; Byakika-Kibwika, Pauline ; Okaba-Kayom, Violet ; Flaherty, John P. ; Boffito, Marta ; Namakula, Rhoda ; Ryan, Mairin ; Nakabiito, Clemensia ; Back, David J. ; Khoo, Saye ; Merry, Concepta ; Scarsi, Kimberly K. / Suboptimal nevirapine steady-state pharmacokinetics during intrapartum compared with postpartum in HIV-1-seropositive Ugandan women. In: Journal of Acquired Immune Deficiency Syndromes. 2010 ; Vol. 55, No. 3. pp. 345-350.
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abstract = "Background: Conflicting data exist regarding the effect of pregnancy on steady-state nevirapine pharmacokinetics (PK), although steady-state nevirapine concentrations during pregnancy have never been characterized in sub-Saharan Africa. Methods: This was a longitudinal intensive PK study in Ugandan pregnant women receiving nevirapine-based antiretroviral therapy. Participants underwent intensive 12-hour PK sampling during the second trimester (T2; n = 4), third trimester (T3; n = 15) and 6 weeks postpartum (PP; n = 15). HIV-1 RNA was performed within 2 weeks of each visit. Nevirapine C12 above 3000 ng/mL was classified as optimal based on the suggested value for therapeutic drug monitoring. Results: The pharmacokinetics of nevirapine were influenced by pregnancy, demonstrated by a 20{\%} reduction in the maximum concentration, minimum concentration (C12), and area under the curve between T3 and PP visits (P = 0.001, P = 0.011 and P = 0.005, respectively). Ten subjects (66.7{\%}) had C12 values <3000 ng/mL during T3. Of these participants, 7 partcipant's C12 concentrations increased to >3000 ng/mL during the PP visit. HIV-1 RNA were <1000 copies per milliliter at T3 and <400 copies per milliliter at PP in all patients. Conclusions: Nevirapine exposure was reduced in Ugandan women during their third trimester compared with the same women PP, however, HIV RNA remained <1000 copies per milliliter. The long-term impact of intermittent suboptimal nevirapine concentrations during pregnancy is unknown.",
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T1 - Suboptimal nevirapine steady-state pharmacokinetics during intrapartum compared with postpartum in HIV-1-seropositive Ugandan women

AU - Lamorde, Mohammed

AU - Byakika-Kibwika, Pauline

AU - Okaba-Kayom, Violet

AU - Flaherty, John P.

AU - Boffito, Marta

AU - Namakula, Rhoda

AU - Ryan, Mairin

AU - Nakabiito, Clemensia

AU - Back, David J.

AU - Khoo, Saye

AU - Merry, Concepta

AU - Scarsi, Kimberly K.

PY - 2010/11/1

Y1 - 2010/11/1

N2 - Background: Conflicting data exist regarding the effect of pregnancy on steady-state nevirapine pharmacokinetics (PK), although steady-state nevirapine concentrations during pregnancy have never been characterized in sub-Saharan Africa. Methods: This was a longitudinal intensive PK study in Ugandan pregnant women receiving nevirapine-based antiretroviral therapy. Participants underwent intensive 12-hour PK sampling during the second trimester (T2; n = 4), third trimester (T3; n = 15) and 6 weeks postpartum (PP; n = 15). HIV-1 RNA was performed within 2 weeks of each visit. Nevirapine C12 above 3000 ng/mL was classified as optimal based on the suggested value for therapeutic drug monitoring. Results: The pharmacokinetics of nevirapine were influenced by pregnancy, demonstrated by a 20% reduction in the maximum concentration, minimum concentration (C12), and area under the curve between T3 and PP visits (P = 0.001, P = 0.011 and P = 0.005, respectively). Ten subjects (66.7%) had C12 values <3000 ng/mL during T3. Of these participants, 7 partcipant's C12 concentrations increased to >3000 ng/mL during the PP visit. HIV-1 RNA were <1000 copies per milliliter at T3 and <400 copies per milliliter at PP in all patients. Conclusions: Nevirapine exposure was reduced in Ugandan women during their third trimester compared with the same women PP, however, HIV RNA remained <1000 copies per milliliter. The long-term impact of intermittent suboptimal nevirapine concentrations during pregnancy is unknown.

AB - Background: Conflicting data exist regarding the effect of pregnancy on steady-state nevirapine pharmacokinetics (PK), although steady-state nevirapine concentrations during pregnancy have never been characterized in sub-Saharan Africa. Methods: This was a longitudinal intensive PK study in Ugandan pregnant women receiving nevirapine-based antiretroviral therapy. Participants underwent intensive 12-hour PK sampling during the second trimester (T2; n = 4), third trimester (T3; n = 15) and 6 weeks postpartum (PP; n = 15). HIV-1 RNA was performed within 2 weeks of each visit. Nevirapine C12 above 3000 ng/mL was classified as optimal based on the suggested value for therapeutic drug monitoring. Results: The pharmacokinetics of nevirapine were influenced by pregnancy, demonstrated by a 20% reduction in the maximum concentration, minimum concentration (C12), and area under the curve between T3 and PP visits (P = 0.001, P = 0.011 and P = 0.005, respectively). Ten subjects (66.7%) had C12 values <3000 ng/mL during T3. Of these participants, 7 partcipant's C12 concentrations increased to >3000 ng/mL during the PP visit. HIV-1 RNA were <1000 copies per milliliter at T3 and <400 copies per milliliter at PP in all patients. Conclusions: Nevirapine exposure was reduced in Ugandan women during their third trimester compared with the same women PP, however, HIV RNA remained <1000 copies per milliliter. The long-term impact of intermittent suboptimal nevirapine concentrations during pregnancy is unknown.

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