Mefloquine disposition in normals and in patients with severePlasmodium falciparum malaria

Juma, Francis D.; Ogeto, J. O.

doi:10.1007/bf03190836

Cited by 19 publications

(10 citation statements)

References 4 publications

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“…Karbwang et al [1] found plasma concentrations in healthy Thai volunteers to be twice as high as those reported by Riviere et al [2] in healthy Caucasian volunteers. In contrast, a study by Juma et al [3] [2].…”

contrasting

confidence: 40%

Whole blood concentrations of mefloquine enantiomers in healthy Thai volunteers

Martin

Gimenez

Bangchang

et al. 1994

Eur J Clin Pharmacol

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We studied the pharmacokinetics of the enantiomers of mefloquine in whole blood in healthy Thai volunteers after administration of a single oral dose of 750 mg of the racemic mixture. Mefloquine pharmacokinetics were stereoselective. The peak concentrations and areas under the curve of the (-) enantiomer were significantly higher than those of its antipode (0.79 versus 0.46 microgram.ml-1 and 402 versus 94 micrograms.h.ml-1). The half-lives of (-)MQ were significantly longer than those of (+)MQ (531 versus 206 h). No stereoselectivity was observed for tmax values.

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contrasting

confidence: 40%

Whole blood concentrations of mefloquine enantiomers in healthy Thai volunteers

Martin

Gimenez

Bangchang

et al. 1994

Eur J Clin Pharmacol

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“…Mean residence times were also very similar to those reported previously; 15.3 (4.7) days compared with 15.5 (3.1) days in Thai adults with uncomplicated malaria (Karbwang et al, 1988a (Karbwang et al, 1988a,b) and are comparable with the estimates in children in this study; mean (s.d.) CLpO 0.52 (0.27) ml kg-' min-', whereas in African adults with more severe malaria (Juma & Ogeto, 1989) estimates were much higher; mean CLp. was 0.89 ml kg-' min-'.…”

Section: Discussionmentioning

confidence: 90%

“…The pharmacokinetic properties of mefloquine have been defined in adults with acute malaria (Juma & Ogeto, 1989;Karbwang et al, 1988a,b;Looareesuwan et al, 1987) but not in children. We have conducted a prospective study of the pharmacokinetic properties of mefloquine in 12 children with acute uncomplicated falciparum malaria living on the Thai-Burmese border.…”

Section: Introductionmentioning

confidence: 99%

Mefloquine pharmacokinetics and resistance in children with acute falciparum malaria.

Nosten

Kuile

Chongsuphajaisiddhi

et al. 1991

Brit J Clinical Pharma

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The pharmacokinetic properties of mefloquine hydrochloride (15 mg base kg-l) were studied in 12 Karen children (five girls, seven boys) aged between 5 and 10 years presenting with uncomplicated falciparum malaria. The drug was well tolerated. Mean (s.d.) peak blood drug concentrations of 2031 (831) ng ml-n were reached in a median of 8 (range 6-24) h. Mean (s.d.) estimates for oral clearance and mean residence time were 0.52 (0.27) ml min-' kg-' and 15.3 (4.7) days, respectively. These values are similar to those reported previously in adults. In one child parasitaemia failed to clear despite whole blood mefloquine concentrations which peaked at 1744 ng ml-1; parasitaemia rose and fever recurred when blood drug concentrations had fallen to 442 ng ml-1. The prevalence of highly mefloquine resistant parasites such as this can be expected to increase under drug pressure in this area.

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“…Because mefloquine is an antimalarial, the in vivo human PK profile is known. Mefloquine and its metabolites are excreted slowly from the body through faeces and urine [38,41] with a terminal elimination half-life of roughly three weeks in healthy subjects, 10 to 14 days in malaria patients with uncomplicated falciparum malaria [42,43] and approximately 20 days in cases involving more severe malaria [43,44]. Its only reported use in veterinary medicine has been as an antimalarial drug for raptors [45].…”

Section: Plos Onementioning

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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Mefloquine disposition in normals and in patients with severePlasmodium falciparum malaria

Cited by 19 publications

References 4 publications

Whole blood concentrations of mefloquine enantiomers in healthy Thai volunteers

Whole blood concentrations of mefloquine enantiomers in healthy Thai volunteers

Mefloquine pharmacokinetics and resistance in children with acute falciparum malaria.

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

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