Pharmacokinetic interactions between artesunate-mefloquine and ritonavir-boosted lopinavir in healthy Thai adults

Rattanapunya, Siwalee; Cressey, Tim R.; Rueangweerayut, Ronnatrai; Tawon, Yardpiroon; Kongjam, Panida; Na‐Bangchang, Kesara

doi:10.1186/s12936-015-0916-8

Cited by 15 publications

(7 citation statements)

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“…In addition, the existing information is mainly limited to artemisinin derivatives [ 37 , 38 ]. A recent study reported potential pharmacokinetic interactions between MQ-Artesunate (MQ-AS) and lopinavir (LPV/r) in adults, with a reduction in systemic exposure of both drug combinations, suggesting a higher risk of treatment failure for both malaria and HIV infection when the two drugs are co-administered [ 39 ]. Another limitation of our study was that data on adherence and on average duration of ARV drugs administration before delivery, which are known to determine viral suppression, was not available.…”

Section: Discussionmentioning

confidence: 99%

HIV drug resistance patterns in pregnant women using next generation sequence in Mozambique

et al. 2018

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BackgroundFew data on HIV resistance in pregnancy are available from Mozambique, one of the countries with the highest HIV toll worldwide. Understanding the patterns of HIV drug resistance in pregnant women might help in tailoring optimal regimens for prevention of mother to child transmission of HIV (pMTCT) and antenatal care.ObjectivesTo describe the frequency and characteristics of HIV drug resistance mutations (HIVDRM) in pregnant women with virological failure at delivery, despite pMTCT or antiretroviral therapy (ART).MethodsSamples from HIV-infected pregnant women from a rural area in southern Mozambique were analysed. Only women with HIV-1 RNA >400c/mL at delivery were included in the analysis. HIVDRM were determined using MiSeq® (detection threshold 1%) at the first antenatal care (ANC) visit and at the time of delivery.ResultsNinety and 60 samples were available at the first ANC visit and delivery, respectively. At first ANC, 97% of the women had HIV-1 RNA>400c/mL, 39% had CD4+ counts <350 c/mm3 and 30% were previously not on ART. Thirteen women (14%) had at least one HIVDRM of whom 70% were not on previous ART. Eight women (13%) had at least one HIVDRM at delivery. Out of 37 women with data available from the two time points, 8 (21%) developed at least one new HIVDRM during pMTCT or ART. Twenty seven per cent (53/191), 32% (44/138) and 100% (5/5) of the mutations that were present at enrolment, delivery and that emerged during pregnancy, respectively, were minority mutations (frequency <20%).ConclusionsEven with ultrasensitive HIV-1 genotyping, less than 20% of women with detectable viremia at delivery had HIVDRM before initiating pMTCT or ART. This suggests that factors other than pre-existing resistance, such as lack of adherence or interruptions of the ANC chain, are also relevant to explain lack of virological suppression at the time of delivery in women receiving antiretrovirals drugs during pregnancy.

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Section: Discussionmentioning

confidence: 99%

HIV drug resistance patterns in pregnant women using next generation sequence in Mozambique

et al. 2018

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“…In addition, the analysis showed that mutation of the Kelch-13 propeller did not affect the pharmacokinetic parameters of mefloquine. The significant influence of artesunate administration on mefloquine pharmacokinetics is unlikely [ 45 , 46 ] and was not included in the analysis.…”

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics of mefloquine given as a 3-day artesunate–mefloquine in patients with acute uncomplicated Plasmodium falciparum malaria in a multidrug-resistant area along the Thai–Myanmar border

Hoglund

Ruengweerayut

Na‐Bangchang

2018

Malar J

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BackgroundLow mefloquine exposure has been shown to contribute to treatment failure in patients with uncomplicated falciparum malaria following a 3-day artesunate–mefloquine combination. The present study aimed to develop a population pharmacokinetic model for mefloquine based on whole blood concentration–time profiles of this target population for further dose optimization.MethodsA total of 129 Burmese patients aged above 15 years who presented with typical symptoms of malaria and had a blood smear positive for Plasmodium falciparum were included in the study. All were treated with the standard 3-day combination regimen of artesunate and mefloquine consisting of mefloquine for 2 days and artesunate for 3 days. Blood samples were collected before and at different time points after drug administration from different sub-groups of patients. Mefloquine concentrations were quantified in whole blood using high-performance liquid chromatography. A non-linear mixed-effect modelling approach was applied for population pharmacokinetic analysis using the NONMEM v7.3 software. Covariates investigated (body weight, gender, admission parasitaemia, and molecular markers of mefloquine resistance) were investigated in a step-wise manner using the SCM functionality in Perl-Speaks-NONMEM.ResultsPopulation pharmacokinetic analysis of mefloquine was performed in all patients with a total of 653 samples. Whole blood mefloquine concentration–time profiles were described by a two-compartment disposition model. Of the covariates investigated, none was found to have a significant impact on the pharmacokinetics of mefloquine. Significant differences in maximum concentration (Cmax) and elimination half-life (t1/2) were found in patients who had treatment failure (36 cases) compared to patients with successful treatment (107 cases).ConclusionThe study successfully describes the pharmacokinetics of mefloquine following a 2-day treatment of mefloquine as a part of a 3-day artesunate–mefloquine in patients with uncomplicated falciparum malaria from Thailand. A model has been developed which adequately describes the pharmacokinetics of mefloquine. More extensive clinical studies including both adults and children are needed to fully characterize the pharmacokinetics of mefloquine.

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“…Some of the above potential interactions have been confirmed in pharmacokinetic studies involving ARV drugs and ACTs. [73][74][75][76] Clinical studies are required to determine the impact of these interactions on parasitaemia, efficacy and toxicity of antimalarial therapy in adult population of HIV-infected patients with malaria co-morbidity.…”

Section: Potential Csdis Between Arvs and Antimicrobial Drugsmentioning

confidence: 99%

Clinically Significant Drug-Drug Interaction in a Large Antiretroviral Treatment Centre in Lagos, Nigeria

Oreagba

Usman²,

Oshikoya³

et al. 2019

J Popl Ther Clin Pharmacol

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Background: An important cause of treatment failure to antiretroviral therapy (ART) is the potential interaction between the antiretroviral (ARV) drugs and co-prescribed drugs used concomitantly for the treatment of opportunistic infections and co-morbid ailments in HIV-infected patients. Objectives: The study evaluated potential clinically significant drug interactions (CSDIs) occurring between recommended ART regimens and their co-prescribed non-antiretroviral drugs (CPD) Method: This study was carried out in a large HIV treatment centre (APIN clinic) in a Nigerian teaching hospital, in Lagos Nigeria, caring for over 20,000 registered patients. Electronic Medical Records (EMR) of 500 patients who received treatment between 2005 and 2015, were selected using systematic random sampling, reviewed retrospectively, and evaluated for potential CSDIs using Liverpool HIV Pharmacology Database and other similar databases. Results: Majority of patients, 421 (84%) were at risk of CSDIs, of which 410, (82%) were moderate and frequently involved co-trimoxazole + zidovudine (or stavudine) /lamivudine (386, 77.2%) and NNRTIs or PIs + artemisinin-based combination therapies (ACTs) [296, 59.2%]. Age (p=0.131), sex (p=0.316) and baseline CD4+ cell counts (p>0.05) were not significantly associated with CSDIs. The interactions, however, were significantly associated with the development of antiretroviral treatment failure (p <0.001) which occurred in nearly a third (139; 27.8%) of the patients. Conclusion: There is a high prevalence of CSDIs between ART and CPDs most of which were categorized as moderate. Further studies are required to evaluate the pharmacokinetic and clinical relevance of these interactions.

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Pharmacokinetic interactions between artesunate-mefloquine and ritonavir-boosted lopinavir in healthy Thai adults

Cited by 15 publications

References 68 publications

HIV drug resistance patterns in pregnant women using next generation sequence in Mozambique

HIV drug resistance patterns in pregnant women using next generation sequence in Mozambique

Population pharmacokinetics of mefloquine given as a 3-day artesunate–mefloquine in patients with acute uncomplicated Plasmodium falciparum malaria in a multidrug-resistant area along the Thai–Myanmar border

Clinically Significant Drug-Drug Interaction in a Large Antiretroviral Treatment Centre in Lagos, Nigeria

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