Patient age does not affect mefloquine concentrations in erythrocytes and plasma during the acute phase of falciparum malaria

Vieira, José Luiz Fernandes; Borges, Larissa Maria Guimarães; Ferreira, Michelle Valéria Dias; Rivera, Juan Gonzalo Bardález; Gomes, Margarete do Socorro Mendonça

doi:10.1016/j.bjid.2016.07.005

Cited by 5 publications

(5 citation statements)

References 19 publications

(25 reference statements)

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“…Moreover, artesunate induces severer mitochondrial injury that is mediated by ROS ( 9 ). A previous study has proven that artesunate has an effect on the therapy of cerebral malaria during its acute phase ( 10 ), but whether artesunate affects cerebral infarction is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Protectiveness of Artesunate Given Prior Ischemic Cerebral Infarction Is Mediated by Increased Autophagy

Shao¹,

Shen²,

Sun³

et al. 2018

Front. Neurol.

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Background: Ischemic cerebral infarction is a severe clinical condition that can cause serious mortality. Artesunate, an anti-malarial drug that is widely used in cancer treatment, is known to facilitate accelerated cell apoptosis. The aim of this study is to explore the possible neuroprotective effects of artesunate on hypoxic-ischemic cells in rats.Methods: Middle cerebral artery occlusion (MCAO) rats were treated with artesunate in different doses to observe their survival rate. Primary hippocampal neurons were deprived of oxygen-glucose to induce ischemia symptoms. Western blot was performed to determine the protein expressions of p-mTOR, Beclin-1, and Mcl-1. A five-point scale was used to detect neurological deficit. Cell apoptosis was measured using a TUNEL assay.Results: Artesunate supplementation protected MCAO rats from death and ameliorated brain injury among them. Artesunate administration decreased the expression of p-mTOR, increased the expressions of Beclin-1 and Mcl-1, and decreased the activity of caspase-3 in both the rats' ischemia cerebral cortices and their primary ischemia hippocampal neurons when compared with artesunate-absent ischemic brains and cells. The neuroprotective effects of artesunate were abolished by either leucine (LEU) or 3-MA, while the effects of rapamycin were reversed by 3-MA. In vivo experiments verified the protective effects of artesunate on brain-infarct rats.Conclusion: The results indicate the protectiveness of artesunate against ischemic cerebral infarction, whereas the protectiveness might increase autophagy through regulating the activity of mTOR.

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Section: Introductionmentioning

confidence: 99%

Protectiveness of Artesunate Given Prior Ischemic Cerebral Infarction Is Mediated by Increased Autophagy

Shao¹,

Shen²,

Sun³

et al. 2018

Front. Neurol.

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“…Its only reported use in veterinary medicine has been as an antimalarial drug for raptors [45]. However, mefloquine's exact mechanisms of action as an antimalarial agent and/or as an antiviral agent are unknown [8,46,47].…”

Section: Plos Onementioning

confidence: 99%

“…The antimalarial drug mefloquine is currently used for both prevention (as a monotherapy) and treatment (either alone, or in combination with artesunate) of chloroquine-resistant Plasmodium falciparum malaria in humans [6][7][8]. It was found to substantially reduce the viral load of FIPV and feline calicivirus (FCV) at low concentrations in infected Crandell Rees feline kidney cells without cytotoxic effects [9,10].…”

Section: Introductionmentioning

confidence: 99%

In vitro hepatic metabolism of mefloquine using microsomes from cats, dogs and the common brush-tailed possum (Trichosurus vulpecula)

Izes¹,

Kimble²,

Norris³

et al. 2020

PLoS ONE

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Feline infectious peritonitis (FIP) is a systemic, fatal, viral-induced, immune-mediated disease of cats caused by feline infectious peritonitis virus (FIPV). Mefloquine, a human antimalarial agent, has been shown to inhibit FIPV in vitro. As a first step to evaluate its efficacy and safety profile as a potential FIP treatment for cats, mefloquine underwent incubation in feline, canine and common brush-tailed possum microsomes and phase I metabolism cofactors to determine its rate of phase I depletion. Tramadol was used as a phase I positive control as it undergoes this reaction in both dogs and cats. Using the substrate depletion method, the in vitro intrinsic clearance (mean ± S.D.) of mefloquine by pooled feline and common brush-tailed possum microsomes was 4.5 ± 0.35 and 18.25 ± 3.18 μL/min/mg protein, respectively. However, phase I intrinsic clearance was too slow to determine with canine microsomes. Liquid chromatography-mass spectrometry (LC-MS) identified carboxymefloquine in samples generated by feline microsomes as well as negative controls, suggesting some mefloquine instability. Mefloquine also underwent incubation with feline, canine and common brush-tailed possum microsomes and phase II glucuronidative metabolism cofactors. O-desmethyltramadol (ODMT or M1) was used as a positive control as it undergoes a phase II glucuronidation reaction in these species. The rates of phase II mefloquine depletion by microsomes by all three species were too slow to estimate. Therefore mefloquine likely undergoes phase I hepatic metabolism catalysed by feline and common brush-tailed possum microsomes but not phase II glucuronidative metabolism in all three species and mefloquine is not likely to have delayed elimination in cats with clinically normal, hepatic function. OPEN ACCESSCitation: Izes AM, Kimble B, Norris JM, Govendir M (2020) In vitro hepatic metabolism of mefloquine using microsomes from cats, dogs and the common brush-tailed possum (Trichosurus vulpecula). PLoS ONE 15(4): e0230975. https://doi.

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“…However, an increase in volume of distribution and prolonged half-life were not observed in the older cats (Cats A, B, C and G). In humans, while mefloquine blood concentrations during pregnancy are lower than those in non-pregnant adults, no age-related differences in mefloquine plasma concentrations were found in pharmacokinetic profiles [ 55 , 56 ]. Interestingly, the maximum blood concentrations are 2–3 times higher in Asian adults compared to non-Asian volunteers, the reason for this ethnic difference is unclear [ 30 , 57 ].…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Profile of Oral Administration of Mefloquine to Clinically Normal Cats: A Preliminary In-Vivo Study of a Potential Treatment for Feline Infectious Peritonitis (FIP)

Kimble

Norris

et al. 2020

Animals

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The pharmacokinetic profile of mefloquine was investigated as a preliminary study towards a potential treatment for feline coronavirus infections (such as feline infectious peritonitis) or feline calicivirus infections. Mefloquine was administered at 62.5 mg orally to seven clinically healthy cats twice weekly for four doses and mefloquine plasma concentrations over 336 h were measured using high pressure liquid chromatography (HPLC). The peak plasma concentration (Cmax) after a single oral dose of mefloquine was 2.71 ug/mL and time to reach Cmax (Tmax) was 15 h. The elimination half-life was 224 h. The plasma concentration reached a higher level at 4.06 ug/mL when mefloquine was administered with food. Adverse effects of dosing included vomiting following administration without food in some cats. Mild increases in serum symmetric dimethylarginine (SDMA), but not creatinine, concentrations were observed. Mefloquine may provide a safe effective treatment for feline coronavirus and feline calicivirus infections in cats.

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Patient age does not affect mefloquine concentrations in erythrocytes and plasma during the acute phase of falciparum malaria

Cited by 5 publications

References 19 publications

Protectiveness of Artesunate Given Prior Ischemic Cerebral Infarction Is Mediated by Increased Autophagy

Protectiveness of Artesunate Given Prior Ischemic Cerebral Infarction Is Mediated by Increased Autophagy

In vitro hepatic metabolism of mefloquine using microsomes from cats, dogs and the common brush-tailed possum (Trichosurus vulpecula)

Pharmacokinetic Profile of Oral Administration of Mefloquine to Clinically Normal Cats: A Preliminary In-Vivo Study of a Potential Treatment for Feline Infectious Peritonitis (FIP)

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