Nevirapine-based antiretroviral therapy impacts artesunate and dihydroartemisinin disposition in HIV-infected Nigerian adults

Fatai A. Fehintola, Kimberly K. Scarsi, Qing Ma, Sunil Parikh, Gene D. Morse, Babafemi Taiwo, Ibrahim Tope Akinola, Isaac F. Adewole, Niklas Lindegardh, Aphiradee Phakderaj, Oladosu Ojengbede, Robert L. Murphy, Olusegun O. Akinyinka, Francesca T. Aweeka

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background. Nevirapine- (NVP-) based antiretroviral therapy (ART) and artesunate-amodiaquine are frequently coprescribed in areas of HIV and malaria endemicity. We explored the impact of this practice on artesunate and dihydroartemisinin pharmacokinetics. Methods. We conducted a parallel-group pharmacokinetic comparison between HIV-infected patients receiving NVP-based ART (n=10) and ART-naive controls (n=11). Artesunate-amodiaquine 200/600 mg was given daily for three days. Measurement of drug concentrations occurred between 0 and 96 hours after the final dose. Pharmacokinetic parameters were determined using noncompartmental analysis. Results. Comparing the NVP group to controls, clearance of artesunate was reduced 50% (1950 versus 2995 L/h; P=0.03), resulting in a 45% increase in the AUC(105 versus 69 ug hr/L; P=0.02). The half-life of dihydroartemisinin was shorter in the NVP group (1.6 versuss 3.2 h; P=0.004), but other dihydroartemisinin pharmacokinetic parameters were unchanged. A lower conversion of artesunate to dihydroartemisinin was observed in the NVP group (dihydroartemisinin: artesunate AUC=5.6 versuss 8.5 in NVP and control groups, respectively, P=0.008). Conclusion. Although NVP-containing ART impacted some pharmacokinetic parameters of artesunate and dihydroartemisinin, overall exposure was similar or better in the NVP group.

Original languageEnglish (US)
Article number703604
JournalAIDS Research and Treatment
Volume2012
DOIs
StatePublished - Dec 1 2012

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dihydroartemisinin
Nevirapine
HIV
Pharmacokinetics
Area Under Curve
Therapeutics
Control Groups
Malaria
Half-Life
artesunate

ASJC Scopus subject areas

  • Immunology and Allergy
  • Dermatology
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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Nevirapine-based antiretroviral therapy impacts artesunate and dihydroartemisinin disposition in HIV-infected Nigerian adults. / Fehintola, Fatai A.; Scarsi, Kimberly K.; Ma, Qing; Parikh, Sunil; Morse, Gene D.; Taiwo, Babafemi; Akinola, Ibrahim Tope; Adewole, Isaac F.; Lindegardh, Niklas; Phakderaj, Aphiradee; Ojengbede, Oladosu; Murphy, Robert L.; Akinyinka, Olusegun O.; Aweeka, Francesca T.

In: AIDS Research and Treatment, Vol. 2012, 703604, 01.12.2012.

Research output: Contribution to journalArticle

Fehintola, FA, Scarsi, KK, Ma, Q, Parikh, S, Morse, GD, Taiwo, B, Akinola, IT, Adewole, IF, Lindegardh, N, Phakderaj, A, Ojengbede, O, Murphy, RL, Akinyinka, OO & Aweeka, FT 2012, 'Nevirapine-based antiretroviral therapy impacts artesunate and dihydroartemisinin disposition in HIV-infected Nigerian adults', AIDS Research and Treatment, vol. 2012, 703604. https://doi.org/10.1155/2012/703604
Fehintola, Fatai A. ; Scarsi, Kimberly K. ; Ma, Qing ; Parikh, Sunil ; Morse, Gene D. ; Taiwo, Babafemi ; Akinola, Ibrahim Tope ; Adewole, Isaac F. ; Lindegardh, Niklas ; Phakderaj, Aphiradee ; Ojengbede, Oladosu ; Murphy, Robert L. ; Akinyinka, Olusegun O. ; Aweeka, Francesca T. / Nevirapine-based antiretroviral therapy impacts artesunate and dihydroartemisinin disposition in HIV-infected Nigerian adults. In: AIDS Research and Treatment. 2012 ; Vol. 2012.
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title = "Nevirapine-based antiretroviral therapy impacts artesunate and dihydroartemisinin disposition in HIV-infected Nigerian adults",
abstract = "Background. Nevirapine- (NVP-) based antiretroviral therapy (ART) and artesunate-amodiaquine are frequently coprescribed in areas of HIV and malaria endemicity. We explored the impact of this practice on artesunate and dihydroartemisinin pharmacokinetics. Methods. We conducted a parallel-group pharmacokinetic comparison between HIV-infected patients receiving NVP-based ART (n=10) and ART-naive controls (n=11). Artesunate-amodiaquine 200/600 mg was given daily for three days. Measurement of drug concentrations occurred between 0 and 96 hours after the final dose. Pharmacokinetic parameters were determined using noncompartmental analysis. Results. Comparing the NVP group to controls, clearance of artesunate was reduced 50{\%} (1950 versus 2995 L/h; P=0.03), resulting in a 45{\%} increase in the AUC(105 versus 69 ug hr/L; P=0.02). The half-life of dihydroartemisinin was shorter in the NVP group (1.6 versuss 3.2 h; P=0.004), but other dihydroartemisinin pharmacokinetic parameters were unchanged. A lower conversion of artesunate to dihydroartemisinin was observed in the NVP group (dihydroartemisinin: artesunate AUC=5.6 versuss 8.5 in NVP and control groups, respectively, P=0.008). Conclusion. Although NVP-containing ART impacted some pharmacokinetic parameters of artesunate and dihydroartemisinin, overall exposure was similar or better in the NVP group.",
author = "Fehintola, {Fatai A.} and Scarsi, {Kimberly K.} and Qing Ma and Sunil Parikh and Morse, {Gene D.} and Babafemi Taiwo and Akinola, {Ibrahim Tope} and Adewole, {Isaac F.} and Niklas Lindegardh and Aphiradee Phakderaj and Oladosu Ojengbede and Murphy, {Robert L.} and Akinyinka, {Olusegun O.} and Aweeka, {Francesca T.}",
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T1 - Nevirapine-based antiretroviral therapy impacts artesunate and dihydroartemisinin disposition in HIV-infected Nigerian adults

AU - Fehintola, Fatai A.

AU - Scarsi, Kimberly K.

AU - Ma, Qing

AU - Parikh, Sunil

AU - Morse, Gene D.

AU - Taiwo, Babafemi

AU - Akinola, Ibrahim Tope

AU - Adewole, Isaac F.

AU - Lindegardh, Niklas

AU - Phakderaj, Aphiradee

AU - Ojengbede, Oladosu

AU - Murphy, Robert L.

AU - Akinyinka, Olusegun O.

AU - Aweeka, Francesca T.

PY - 2012/12/1

Y1 - 2012/12/1

N2 - Background. Nevirapine- (NVP-) based antiretroviral therapy (ART) and artesunate-amodiaquine are frequently coprescribed in areas of HIV and malaria endemicity. We explored the impact of this practice on artesunate and dihydroartemisinin pharmacokinetics. Methods. We conducted a parallel-group pharmacokinetic comparison between HIV-infected patients receiving NVP-based ART (n=10) and ART-naive controls (n=11). Artesunate-amodiaquine 200/600 mg was given daily for three days. Measurement of drug concentrations occurred between 0 and 96 hours after the final dose. Pharmacokinetic parameters were determined using noncompartmental analysis. Results. Comparing the NVP group to controls, clearance of artesunate was reduced 50% (1950 versus 2995 L/h; P=0.03), resulting in a 45% increase in the AUC(105 versus 69 ug hr/L; P=0.02). The half-life of dihydroartemisinin was shorter in the NVP group (1.6 versuss 3.2 h; P=0.004), but other dihydroartemisinin pharmacokinetic parameters were unchanged. A lower conversion of artesunate to dihydroartemisinin was observed in the NVP group (dihydroartemisinin: artesunate AUC=5.6 versuss 8.5 in NVP and control groups, respectively, P=0.008). Conclusion. Although NVP-containing ART impacted some pharmacokinetic parameters of artesunate and dihydroartemisinin, overall exposure was similar or better in the NVP group.

AB - Background. Nevirapine- (NVP-) based antiretroviral therapy (ART) and artesunate-amodiaquine are frequently coprescribed in areas of HIV and malaria endemicity. We explored the impact of this practice on artesunate and dihydroartemisinin pharmacokinetics. Methods. We conducted a parallel-group pharmacokinetic comparison between HIV-infected patients receiving NVP-based ART (n=10) and ART-naive controls (n=11). Artesunate-amodiaquine 200/600 mg was given daily for three days. Measurement of drug concentrations occurred between 0 and 96 hours after the final dose. Pharmacokinetic parameters were determined using noncompartmental analysis. Results. Comparing the NVP group to controls, clearance of artesunate was reduced 50% (1950 versus 2995 L/h; P=0.03), resulting in a 45% increase in the AUC(105 versus 69 ug hr/L; P=0.02). The half-life of dihydroartemisinin was shorter in the NVP group (1.6 versuss 3.2 h; P=0.004), but other dihydroartemisinin pharmacokinetic parameters were unchanged. A lower conversion of artesunate to dihydroartemisinin was observed in the NVP group (dihydroartemisinin: artesunate AUC=5.6 versuss 8.5 in NVP and control groups, respectively, P=0.008). Conclusion. Although NVP-containing ART impacted some pharmacokinetic parameters of artesunate and dihydroartemisinin, overall exposure was similar or better in the NVP group.

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DO - 10.1155/2012/703604

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