Browsing by Author "Back, David"

Now showing 1 - 7 of 7
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    Cardiac Conduction Safety during Coadministration of Artemether-Lumefantrine and Lopinavir/Ritonavir in HIV-Infected Ugandan Adults
    (Chemotherapy research and practice, 2011) Byakika-Kibwika, Pauline; Lamorde, Mohammed; Lwabi, Peter; Nyakoojo, Wilson B.; Okaba-Kayom, Violet; Mayanja-Kizza, Harriet; Boffito, Marta; Katabira, Elly; Back, David; Khoo, Saye; Merry, Concepta
    We aimed to assess cardiac conduction safety of coadministration of the CYP3A4 inhibitor lopinavir/ritonavir (LPV/r) and the CYP3A4 substrate artemether-lumefantrine (AL) in HIV-positive Ugandans. Methods. Open-label safety study of HIV positive adults administered single-dose AL (80/400 mg) alone or with LPV/r (400/100 mg). Cardiac function was monitored using continuous electrocardiograph (ECG). Results. Thirty-two patients were enrolled; 16 taking LPV/r -based ART and 16 ART naıve. All took single dose AL. No serious adverse events were observed. ECG parameters in milliseconds remained within normal limits. QTc measurements did not change significantly over 72 hours although were higher in LPV/r arm at 24 (424 versus 406; P = .02) and 72 hours (424 versus 408; P = .004) after AL intake. Conclusion. Coadministration of single dose of AL with LPV/r was safe; however, safety of six-dose AL regimen with LPV/r should be investigated.
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    Efavirenz- but not nevirapine-based antiretroviral therapy decreases exposure to the levonorgestrel released from a sub-dermal contraceptive implant
    (Journal of the International AIDS Society, 2014) Kimberly, Scarsi; Lamorde, Mohammed; Darin, Kristin; Dilly Penchala, Sujan; Else, Laura; Nakalema, Shadia; Byakika-Kibwika, Pauline; Khoo, Saye; Cohn, Susan; Merry, Concepta; Back, David
    Sub-dermal hormone implants, such as levonorgestrel (LNG), are a safe and desirable form of long-acting contraception, but their use among HIV-positive women on antiretroviral therapy (ART) may be compromised given the potential for a cytochrome P450 3A-mediated drug-drug interaction. Our study aimed to characterize the pharmacokinetics of LNG released from a sub-dermal implant over six months in HIV-positive Ugandan women on nevirapine (NVP)- or efavirenz (EFV)-based ART.
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    Global patient safety and antiretroviral drug–drug interactions in the resource-limited setting
    (Journal of Antimicrobial Chemotherapy, 2013) Seden, Kay; Khoo, Saye H.; Back, David; Byakika-Kibwika, Pauline; Lamorde, Mohammed; Ryan, Mairin; Merry, Concepta
    Scale-up of HIV treatment services may have contributed to an increase in functional health facilities available in resource-limited settings and an increase in patient use of facilities and retention in care. As more patients are reached with medicines, monitoring patient safety is increasingly important. Limited data from resource limited settings suggest that medication error and antiretroviral drug–drug interactions may pose a significant risk to patient safety. Commonly cited causes of medication error in the developed world include the speed and complexity of the medication use cycle combined with inadequate systems and processes. In resource-limited settings, specific factors may contribute, such as inadequate human resources and high disease burden. Management of drug–drug interactions may be complicated by limited access to alternative medicines or laboratory monitoring. Improving patient safety by addressing the issue of antiretroviral drug–drug interactions has the potential not just to improve healthcare for individuals, but also to strengthen health systems and improve vital communication among healthcare providers and with regulatory agencies.
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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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    Nevirapine pharmacokinetics when initiated at 200 mg or 400 mg daily in HIV-1 and tuberculosis co-infected Ugandan adults on rifampicin
    (Journal of Antimicrobial Chemotherapy, 2011) Lamorde, Mohammed; Byakika-Kibwika, Pauline; Okaba-Kayom, Violet; Ryan, Mairin; Coakley, Peter; Boffito, Marta; Namakula, Rhoda; Kalemeera, Francis; Colebunders, Robert; Back, David; Khoo, Saye; Merry, Concepta
    In resource-poor countries, HIV and tuberculosis (TB) co-infection results in significant morbidity and mortality. Co-treatment is recommended by the WHO;1 however, drug interactions are common between anti-TB regimens containing rifampicin and antiretroviral drugs. In these settings, rifampicin is a key drug for TB treatment because alternative rifamycins are more expensive and usually not available in public TB control programmes. Similarly, for HIV treatment, only a limited number of antiretroviral drugs are routinely used. The problems arising from limited drug options are compounded by the wide use of fixed-dose combination (FDC) formulations for both diseases. When these formulations are used, drug substitutions are not possible and dose adjustments are usually difficult.
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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.
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    Steady-state pharmacokinetics of lopinavir plus ritonavir when administered under different meal conditions in HIV-infected Ugandan adults
    (Journal of acquired immune deficiency syndromes, 2012) Lamorde, Mohammed; Byakika-Kibwika, Pauline; Boffito, Marta; Nabukeera, Lillian; Mayito, Jonathan; Ogwal- Okeng, Jasper; Tjia, John; Back, David; Khoo, Saye; Ryan, Mairin; Merry, Concepta
    We investigated the effect of food on the steady-state pharmacokinetics of lopinavir and ritonavir in 12 Ugandan patients receiving lopinavir co-formulated with ritonavir (LPV/r) tablets using a cross-over design. Intensive pharmacokinetic sampling was performed seven days apart following LPV/r dosing under moderate fat, high fat and fasted meal conditions. Lopinavir and ritonavir concentrations were determined by liquid chromatography and tandem mass spectrometry. Compared to the fasted state, a high fat meal reduced lopinavir and ritonavir area under the curve (AUC) by 14% and 29%, respectively. With a moderate fat meal, AUC for both drugs was similar to the fasted state.