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Lower atovaquone/proguanil concentrations in patients taking efavirenz, lopinavir/ritonavir or atazanavir/ritonavir

Van Luin, Matthijsa,b,c; Van der Ende, Marchina Ed; Richter, Clemense; Visser, Mirjamb; Faraj, Diarif; Van der Ven, Andrec,g; Gelinck, Luch,i; Kroon, Franki; Wit, Ferdinand Wj; Van Schaik, Ron HNk; Kuks, Paul FMb; Burger, David Ma,c

doi: 10.1097/QAD.0b013e3283389129
Research Letters

HIV-infected travellers frequently use atovaquone/proguanil as malaria prophylaxis. We compared atovaquone/proguanil pharmacokinetics between healthy volunteers and HIV-infected patients taking efavirenz, lopinavir/ritonavir or atazanavir/ritonavir. The geometric mean ratio (95% confidence interval) area under the curve (AUC)0→t for atovaquone relative to the healthy volunteers was 0.25 (0.16–0.38), 0.26 (0.17–0.41) and 0.54 (0.35–0.83) for patients on efavirenz, lopinavir/ritonavir and atazanavir/ritonavir, respectively. Proguanil plasma concentrations were also significantly lower (38–43%). Physicians should be alert for atovaquone/proguanil prophylaxis failures in patients taking efavirenz, lopinavir/ritonavir or atazanavir/ritonavir.

aDepartment of Clinical Pharmacy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

bDepartment of Clinical Pharmacy, Rijnstate Hospital, Arnhem, The Netherlands

cNijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

dDepartment of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands

eDepartment of Internal Medicine, Rijnstate Hospital, Arnhem, The Netherlands

fDepartment of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands

gDepartment of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

hDepartment of Medical Microbiology and Infectious Diseases, Erasmus Medical Centre, Rotterdam, The Netherlands

iDepartment of Infectious Diseases, Leiden University Medical Centre, Leiden, The Netherlands

jCentre for Poverty-related Communicable Diseases, Academic Medical Centre, Amsterdam, The Netherlands

kDepartment of Clinical Chemistry, Erasmus Medical Centre, Rotterdam, The Netherlands.

Received 26 November, 2009

Revised 11 December, 2009

Accepted 9 February, 2010

Correspondence to Matthijs van Luin, Department of Clinical Pharmacy, 864 Radboud University Nijmegen Medical Centre, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands. Tel: +31 24 3616405; fax: +31 24 3668755; e-mail: m.vanluin@akf.umcn.nl

© 2010 Lippincott Williams & Wilkins, Inc.