Browsing by Author "Tarning, Joel"

Now showing 1 - 6 of 6
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    Drug Interactions between Dolutegravir and Artemether- Lumefantrine or Artesunate-Amodiaquine
    (Antimicrobial agents and chemotherapy, 2018) Walimbwa, Stephen I.; Lamorde, Mohammed; Waitt, Catriona; Kaboggoza, Julian; Else, Laura; Byakika-Kibwika, Pauline; Amara, Alieu; Gini, Joshua; Winterberg, Markus; Chiong, Justin; Tarning, Joel; Khoob, Saye H.
    Across sub-Saharan Africa, patients with HIV on antiretrovirals often getmalaria and need cotreatment with artemisinin-containing therapies. We undertook two pharmacokinetic studies in healthy volunteers, using standard adult doses of artemetherlumefantrine or artesunate-amodiaquine given with 50mg once daily dolutegravir (DTG) to investigate the drug-drug interaction between artemether-lumefantrine or artesunateamodiaquine and dolutegravir. The dolutegravir/artemether-lumefantrine interaction was evaluated in a two-way crossover study and measured artemether, dihydroartemisinin, lumefantrine, and desbutyl-lumefantrine over 264 h. The dolutegravir/artesunate-amodiaquine interaction was investigated using a parallel study design due to long half-life of the amodiaquine metabolite, desethylamodiaquine and measured artesunate, amodiaquine, and desethylamodiaquine over 624 h.
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    Lopinavir/ritonavir significantly influences pharmacokinetic exposure of artemether/lumefantrine in HIV-infected Ugandan adults
    (Journal of antimicrobial chemotherapy, 2012) Byakika-Kibwika, Pauline; Lamorde, Mohammed; Okaba-Kayom, Violet; Mayanja-Kizza, Harriet; Katabira, Elly; Hanpithakpong, Warunee; Pakker, Nadine; Dorlo, Thomas P. C.; Tarning, Joel; Lindegardh, Niklas; Vries, Peter J. de; Back, David; Khoo, Saye; Merry, Concepta
    Treatment of HIV/malaria-coinfected patients with antiretroviral therapy (ART) and artemisininbased combination therapy has potential for drug interactions. We investigated the pharmacokinetics of artemether, dihydroartemisinin and lumefantrine after administration of a single dose of 80/480 mg of artemether/ lumefantrine to HIV-infected adults, taken with and without lopinavir/ritonavir. Methods: A two-arm parallel study of 13 HIV-infected ART-naive adults and 16 HIV-infected adults stable on 400/100 mg of lopinavir/ritonavir plus two nucleoside reverse transcriptase inhibitors (ClinicalTrials.gov, NCT 00619944). Each participant received a single dose of 80/480 mg of artemether/lumefantrine under continuous cardiac function monitoring. Plasma concentrations of artemether, dihydroartemisinin and lumefantrine were measured.
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    Pharmacokinetics and pharmacodynamics of intravenous artesunate during severe malaria treatment in Ugandan adults
    (Malaria Journal, 2012) Byakika-Kibwika, Pauline; Lamorde, Mohammed; Mayito, Jonathan; Nabukeera, Lillian; Mayanja-Kizza, Harriet; Katabira, Elly; Hanpithakpong, Warunee; Obua, Celestino; Pakker, Nadine; Lindegardh, Niklas; Tarning, Joel; de Vries, Peter J.; Merry, Concepta
    Severe malaria is a medical emergency with high mortality. Prompt achievement of therapeutic concentrations of highly effective anti-malarial drugs reduces the risk of death. The aim of this study was to assess the pharmacokinetics and pharmacodynamics of intravenous artesunate in Ugandan adults with severe malaria. Methods: Fourteen adults with severe falciparum malaria requiring parenteral therapy were treated with 2.4 mg/kg intravenous artesunate. Blood samples were collected after the initial dose and plasma concentrations of artesunate and dihydroartemisinin measured by solid-phase extraction and liquid chromatography-tandem mass spectrometry. The study was approved by the Makerere University Faculty of Medicine Research and Ethics Committee (Ref2010-015) and Uganda National Council of Science and Technology (HS605) and registered with ClinicalTrials.gov (NCT01122134).
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    Piperaquine concentration and malaria treatment outcomes in Ugandan children treated for severe malaria with intravenous Artesunate or quinine plus Dihydroartemisinin-Piperaquine
    (BMC infectious diseases, 2019) Byakika-Kibwika, Pauline; Ssenyonga, Ronald; Lamorde, Mohammed; Blessborn, Daniel; Tarning, Joel
    Treatment for severe malaria must be prompt with effective parenteral antimalarial drugs for at least 24 h to achieve fast parasite clearance, and when the patient can tolerate oral therapy, treatment should be completed with effective artemisinin based combination therapy (ACT) for complete parasite clearance and to prevent recrudescence. We evaluated piperaquine concentration and malaria treatment outcomes among Ugandan children treated for severe malaria with intravenous artesunate (AS) or quinine (QN) plus dihydroartemisininpiperaquine (DP), in Tororo District Hospital in Eastern Uganda.
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    Population pharmacokinetics of Artemether and dihydroartemisinin in pregnant women with uncomplicated Plasmodium falciparum malaria in Uganda
    (Malaria journal, 2012) Tarning, Joel; Kloprogge, Frank; Piola, Patrice; Dhorda, Mehul; Muwanga, Sulaiman; Turyakira, Eleanor; Nuengchamnong, Nitra; Nosten, François; Day, Nicholas P.J.; White, Nicholas J.; Guerin, Philippe J.; Lindegardh, Niklas
    Malaria in pregnancy increases the risk of maternal anemia, abortion and low birth weight. Approximately 85.3 million pregnancies occur annually in areas with Plasmodium falciparum transmission. Pregnancy has been reported to alter the pharmacokinetic properties of many anti-malarial drugs. Reduced drug exposure increases the risk of treatment failure. The objective of this study was to evaluate the population pharmacokinetic properties of artemether and its active metabolite dihydroartemisinin in pregnant women with uncomplicated P. falciparum malaria in Uganda. Methods: Twenty-one women with uncomplicated P. falciparum malaria in the second and third trimesters of pregnancy received the fixed oral combination of 80 mg artemether and 480 mg lumefantrine twice daily for three days. Artemether and dihydroartemisinin plasma concentrations after the last dose administration were quantified using liquid chromatography coupled to tandem mass-spectroscopy. A simultaneous drug-metabolite population pharmacokinetic model for artemether and dihydroartemisinin was developed taking into account different disposition, absorption, error and covariate models. A separate modeling approach and a non-compartmental analysis (NCA) were also performed to enable a comparison with literature values and different modeling strategies. Results: The treatment was well tolerated and there were no cases of recurrent malaria. A flexible absorption model with sequential zero-order and transit-compartment absorption followed by a simultaneous one-compartment disposition model for both artemether and dihydroartemisinin provided the best fit to the data. Artemether and dihydroartemisinin exposure was lower than that reported in non-pregnant populations. An approximately four-fold higher apparent volume of distribution for dihydroartemisinin was obtained by non-compartmental analysis and separate modeling compared to that from simultaneous modeling of the drug and metabolite. This highlights a potential pitfall when analyzing drug/metabolite data with traditional approaches
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    Significant pharmacokinetic interactions between artemether/lumefantrine and efavirenz or nevirapine in HIV-infected Ugandan adults
    (Journal of Antimicrobial Chemotherapy, 2012) Byakika-Kibwika, Pauline; Lamorde, Mohammed; Mayito, Jonathan; Nabukeera, Lillian; Namakula, Rhoda; Mayanja-Kizza, Harriet; Katabira, Elly; Ntale, Muhammad; Pakker, Nadine; Ryan, Mairin; Hanpithakpong, Warunee; Tarning, Joel; Lindegardh, Niklas; Vries, Peter J. de; Khoo, Saye; Back, David
    Co-administration of artemether/lumefantrine with antiretroviral therapy has potential for pharmacokinetic drug interactions. We investigated drug–drug interactions between artemether/lumefantrine and efavirenz or nevirapine. Methods: We performed a cross-over study in which HIV-infected adults received standard six-dose artemether/ lumefantrine 80/480 mg before and at efavirenz or nevirapine steady state. Artemether, dihydroartemisinin, lumefantrine, efavirenz and nevirapine plasma concentrations were measured and compared.