In vitro susceptibility of African isolates of Plasmodium falciparum from Gabon to pyronaridine.

Abstract

Abstract. The in vitro activity of pyronaridine was evaluated against 62 isolates of Plasmodium falciparum from Libreville, Gabon using an isotopic, drug susceptibility microtest and was compared with amodiaquine, chloroquine, quinine, and halofantrine activities. The mean 50% inhibitory concentration (IC 50 ) values of the 62 isolates from Gabon to pyronaridine was 3.0 nM (95% confidence interval [CI] ϭ 2.1-3.9). Pyronaridine was less potent against chloroquine-resistant isolates than chloroquine-susceptible isolates but more potent than chloroquine against chloroquine-resistant parasites. The cut-off value for in vitro reduced susceptibility to pyronaridine was an IC 50 Ͼ 15 nM. Two isolates (3%) showed an IC 50 Ͼ 15 nM. A significant positive correlation was found between the activities of pyronaridine and chloroquine (r 2 ϭ 0.26, P Ͻ 0.001), pyronaridine and quinine (r 2 ϭ 0.36, P Ͻ 0.001), pyronaridine and amodiaquine (r 2 ϭ 0.55, P Ͻ 0.001), and pyronaridine and halofantrine (r 2 ϭ 0.50, P Ͻ 0.001). This correlation suggests in vitro cross-resistance or at least in vitro cross-susceptibility, which is not necessarily predictive of crossresistance in vivo. The present in vitro findings require comparison with those of clinical studies.The only current options for reducing the morbidity and mortality of malaria, especially in Africa, are chemoprophylaxis and chemotherapy. Therefore, the increasing prevalence of strains of Plasmodium falciparum resistant to chloroquine and other antimalarial drugs poses a serious problem for control of malaria.

Antimalarial Efficacy of Hydroxyethylapoquinine (SN-119) and Its Derivatives

“…Similar results were noted for HEQD and HEAQD compared to quinidine. Regarding drug resistance, HEQD and HEAQD demonstrated promising submicromolar activity against quinine-tolerant isolates, with IC 50 s of Ͻ400 nM for Dd2 and below 700 nM for INDO for HEAQD, which are below or within reported cutoffs for quinine tolerance that range from either above 500 or 800 nM (30)(31)(32). Overall, HEQD showed the greatest efficacy in the in vivo model when combined with artesunate, with no adverse side effects being observable in the mice, making it a promising potential alternative to quinine or quinidine as an antimalarial drug.…”

In Vitro Activities of Antibiotics against Plasmodium falciparum Are Inhibited by Iron

“…The isotopic micro drug susceptibility test used in this study was described previously (38 The 50% inhibitory concentration (IC 50 ), i.e., the drug concentration corre-sponding to 50% of the uptake of [ 3 H]hypoxanthine by the parasites in drug-free control wells, was determined by nonlinear regression analysis of log doseresponse curves. Data were analyzed after logarithmic transformation and expressed as the geometric mean IC 50 with 95% confidence intervals.…”

Baseline In Vitro Activities of the Antimalarials Pyronaridine and Methylene Blue against Plasmodium falciparum Isolates from Kenya

“…PRN activity was significantly correlated with those of the quinolone-based drugs PIQ, AQ, DEAQ, and QN but not with CQs (Table 1). PRN in vitro activity was found to correlate with CQ, AQ, or QN in some studies (20,21,23) but not in others (9, 19). We did not find a correlation between PRN and DHA activities, as reported previously (9).…”