Clinical Pharmacokinetic Drug Interactions Associated with Artemisinin Derivatives and HIV-Antivirals

@article{Kiang2013ClinicalPD,
  title={Clinical Pharmacokinetic Drug Interactions Associated with Artemisinin Derivatives and HIV-Antivirals},
  author={Tony K. L. Kiang and Kyle John Wilby and Mary H. H. Ensom},
  journal={Clinical Pharmacokinetics},
  year={2013},
  volume={53},
  pages={141-153}
}
Management of HIV and malaria co-infection is challenging due to potential drug–drug interactions between antimalarial and HIV-antiviral drugs. Little is known of the clinical significance of these drug interactions, and this review provides a comprehensive summary and critical evaluation of the literature. Specifically, drug interactions between WHO-recommended artemisinin combination therapies (ACT) and HIV-antivirals are discussed. An extensive literature search produced eight articles… 
Antiprotozoal and Anthelmintic Agents
TLDR
The potential for interaction between antiparasitics and antiretroviral drugs as there is extensive overlap in patient populations likely infected with both malaria and HIV, which may lead to increased probability of polypharmacy and drug interactions.
Pharmacogenetics of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in resource-limited settings: Influence on antiretroviral therapy response and concomitant anti-tubercular, antimalarial and contraceptive treatments.
  • G. Russo, G. Paganotti, L. Gustafsson
  • Biology, Medicine
    Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases
  • 2016
An overview of pharmacokinetic considerations for the use of artemisinin-based combinations in three unique populations
TLDR
Key topics discussed include pharmacokinetic rationale for combinations of artemisinin agents with partner drugs, implications for dosing considerations with children, Pharmacokinetic changes associated with pregnancy and known clinical pharmacokinetics interactions between antimalarials and other commonly used medications.
A Review of Pharmacogenetics of Antimalarials and Associated Clinical Implications
  • H. Elewa, K. Wilby
  • Biology, Medicine
    European Journal of Drug Metabolism and Pharmacokinetics
  • 2016
TLDR
A need for close monitoring of patients originating from populations where genetic variation in metabolizing enzymes is prevalent is demonstrated, so as to ensure that optimal clinical outcomes are achieved.
Pharmacokinetic interactions between artesunate-mefloquine and ritonavir-boosted lopinavir in healthy Thai adults
TLDR
The reduction in systemic exposure of all investigated drugs raises concerns of an increased risk of treatment failure rate in co-infected patients and should be further investigated.
Use of quantitative pharmacology tools to improve malaria treatments
TLDR
The present review highlights recent clinically-important examples of the ways in which quantitative pharmacology tools have been applied to improve ACT, as well as 8-aminoquinoline use and the characterisation of novel antimalarial therapies such as the spiroindolones.
Pharmacological considerations in the design of anti-malarial drug combination therapies – is matching half-lives enough?
TLDR
There is a restricted pipeline of anti-malarial drugs but awareness of pharmacological design principles during the development stages could optimize CT design pre-deployment, and pharmacokinetic and pharmacodynamic drug interactions and the role of resistance mechanisms are discussed.
Clinical Pharmacokinetics and Drug–Drug Interactions of Elbasvir/Grazoprevir
  • Tony K. L. Kiang
  • Medicine, Biology
    European journal of drug metabolism and pharmacokinetics
  • 2018
TLDR
The available drug–drug interaction data provided some consistency between in vitro and in vivo observations and, in some instances, can provide predictions of likely clinically relevant scenarios.
Pharmacokinetic studies of antimalarials: recent developments
  • T. Davis
  • Biology, Medicine
    Expert review of clinical pharmacology
  • 2016
TLDR
New approaches such as sampling methods involving low volumes and minimal preparation, and population PK analyses which can evaluate the influence of covariates such as age, pregnancy and coadministered therapies, can generate robust data that inform treatment in the most challenging situations in the tropics.
Pharmacotherapy for the prevention of malaria in pregnant women: currently available drugs and challenges
TLDR
The present review summarizes currently available therapies, emerging candidate combination therapies, and the potential challenges to integrating these into mainstream policy.
...
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References

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TLDR
Although clinical studies have so far not shown any significant interactions, drug interactions should be given appropriate attention when other combinations are used, particularly in combination with other agents.
Interaction between Artemether-Lumefantrine and Nevirapine-Based Antiretroviral Therapy in HIV-1-Infected Patients
TLDR
In a parallel-design pharmacokinetic study, concentration-time profiles were obtained in two groups of HIV-infected patients: ART-naïve patients and those stable on nevirapine-based therapy, which decreased artemether and dihydroartemisinin AUCs but unexpectedly increased lumefantrine exposure.
Lopinavir/Ritonavir Affects Pharmacokinetic Exposure of Artemether/Lumefantrine in HIV-Uninfected Healthy Volunteers
TLDR
Coadministration of artmether/lumefantrine and LPV/r can be carried out for patients coinfected with malaria and HIV, and formal safety analysis of concomitant therapy should be addressed by future studies among individuals living in malaria-endemic regions.
Pharmacokinetic and Toxicological Profile of Artemisinin Compounds: An Update
TLDR
The pharmacokinetics and toxicological aspects of artemisinin and its therapeutic implications are discussed, including its propensity for autoinduction, leading to decreased plasma levels on repeated dosing.
Clinical Pharmacology of Artemisinin-Based Combination Therapies
Malaria, a disease transmitted by the female Anopheles mosquito, has had devastating effects on human populations for more than 4000 years. Treatment of the disease with single drugs, such as
Lopinavir/ritonavir significantly influences pharmacokinetic exposure of artemether/lumefantrine in HIV-infected Ugandan adults
TLDR
Co-administration of artemether/lumfantrine with lopinavir/ritonavir significantly increases lumefantrine exposure, but decreases artem ether exposure.
The potential for interactions between antimalarial and antiretroviral drugs
TLDR
At a time when access to antiretroviral drugs is increasing and new combinations of antimalarial drugs are being evaluated it is important that potential interactions between therapies for these two infections are also reviewed.
Concomitant Efavirenz Reduces Pharmacokinetic Exposure to the Antimalarial Drug Artemether–Lumefantrine in Healthy Volunteers
TLDR
Exposure to DHA, but not LR, was significantly lower during EFV-AL co-administration compared with that during administration of AL alone, and these findings may have implications for the treatment efficacy of AL, particularly in children.
In Vitro Activity of Antiretroviral Drugs against Plasmodium falciparum
TLDR
In vitro activity of 19 antiretroviral drugs against the W2 and 3D7 strains of Plasmodium falciparum at concentrations up to 50 μM showed that lopinavir-ritonavir may have clinically relevant antimalarial activity and also enhance the activity of antimalarials.
Nevirapine-Based Antiretroviral Therapy Impacts Artesunate and Dihydroartemisinin Disposition in HIV-Infected Nigerian Adults
TLDR
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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