Malaria is a life-threatening infection caused by the Plasmodium parasite. In 2018 alone, an estimated 219 million cases of malaria were reported globally. One of the growing threats patients face is that the parasite is becoming resistant to drugs called antimalarials.
P218 is a novel drug that is chemoprotective – in other words it protects the body from malaria by minimizing the effect the malaria virus can have on the body. Specifically, it inhibits an enzyme that’s essential for the Plasmodium parasite. The enzyme is also often the target of malaria drugs. But many antimalarial drugs have severe side effects and cause heart issues.
We conducted a study to find out the effects of P218 on the heart of healthy volunteers. Electrocardiograms (ECGs) were performed to record the rhythm, rate, and electrical activity of the heart.
56 volunteers received seven single-ascending doses up to 1000 mg of P218. Participants were randomized to treatment or placebo at a 3:1 ratio. P218 was given in the fasted state with a lunch served 4 hours after dosing. 12-lead ECGs were recorded in triplicate at regular intervals on the test day, and at 48, 72, 120, 168, 192 and 240 hours thereafter. Blood samples were also collected at similar time points to check for pharmacokinetics. Concentration-effect modelling was used to assess the effect of P218 and its metabolites on cardiac intervals.
Our results found that P218 did not prolong the QTcF, J-Tpeak or TpTe intervals at all doses tested. No significant changes in QRS or PR intervals were observed. As such taking P218 orally at a dose of up to 1000 mg does not prolong the QTcF interval and does not significantly change QRS or PR intervals. This suggests that there is a very low risk of drug-induced proarrhythmia with P218.
Learn more about the publication, visit - Concentration-QT modelling of the novel DHFR inhibitor P218 in healthy male volunteers
Authored by Georg Ferber, PhD, Dilshat Djumanov, PhD, Ulrike Lorch, MD, FFPM, Edward Jackson, BSc, MSc, PhD, MBChB, Joao Almeida Melo, James Rickard, MPharm, and Jorg Taubel, MD, FFPM, FESC.
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