# name
Cytochrome P450/ABC transporter inhibition simultaneously
                enhances ivermectin pharmacokinetics in the mammal host and
                pharmacodynamics in Anopheles gambiae

# metadata.dc.description.abstract[].value
Mass administration of endectocides, drugs that kill
                blood-feeding arthropods, has been proposed as a complementary
                strategy to reduce malaria transmission. Ivermectin is one of
                the leading candidates given its excellent safety profile. Here
                we provide proof that the effect of ivermectin can be boosted at
                two different levels by drugs inhibiting the cytochrome or ABC
                transporter in the mammal host and the target mosquitoes. Using
                a mini-pig model, we show that drug-mediated cytochrome P450/ABC
                transporter inhibition results in a 3-fold increase in the time
                ivermectin remains above mosquito-killing concentrations. In
                contrast, P450/ABC transporter induction with rifampicin
                markedly impaired ivermectin absorption. The same
                ketoconazole-mediated cytochrome/ABC transporter inhibition also
                occurs outside the mammal host and enhances the mortality of
                Anopheles gambiae. This was proven by using the samples from the
                mini-pig experiments to conduct an ex-vivo synergistic bioassay
                by membrane-feeding Anopheles mosquitoes. Inhibiting the same
                cytochrome/xenobiotic pump complex in two different organisms to
                simultaneously boost the pharmacokinetic and pharmacodynamic
                activity of a drug is a novel concept that could be applied to
                other systems. Although the lack of a dose-response effect in
                the synergistic bioassay warrants further exploration, our study
                may have broad implications for the control of parasitic and
                vector-borne diseases.

# metadata.dc.source[].value
Articles publicats en revistes (ISGlobal)

# metadata.dc.title[].value
Cytochrome P450/ABC transporter inhibition simultaneously
                enhances ivermectin pharmacokinetics in the mammal host and
                pharmacodynamics in Anopheles gambiae