Halofantrine

Halfan

Pictures

fig1 jpg

There was no significant difference in FCT The 28 day cure rate for halofantrine was significantly greater than for Riamet ® achieves faster parasite clearance Only one patient had a serious side effect directly attributable to a treatment used This was a severe QTc prolongation in the halofantrine group Throughout the

---

fig2 jpg

Riamet ® group QTc increased in 26 of the halofantrine patients No neurological problems were reported for either group Cardiac effects Mean QTc values During this study 8 patients of the 45 treated with Riamet ® experienced recrudescence The following risk factors for this were identified

---

APRD00419 ZOOM gif

---

0703823f1th jpg

Figure 1 Heart rate a and mean arterial blood pressure b measured at various time points in the four groups of anaesthetized rabbits receiving vehicle Control mefloquine MQ halofantrine HF

---

cb2 gif

Figure 4 Clicking in a given region of the scatterplot brings up a sub set of the points to simplify selection

---

0703470f2th jpg

Figure 2 Pulse dependent development of block with 300 nM halofantrine During wash in of halofantrine the cell was held at 80 mV for 3 min without stimulation A series of steps 40 s at 0 mV 20

---

0703823f2th jpg

Figure 2 QTc intervals measured at various time points in the four groups of anaesthetized rabbits receiving vehicle Control mefloquine MQ halofantrine HF or halofantrine after 3 mg kg 1

---

0703823f5th jpg

Figure 5 Correlation between the individual values for QTc intervals measured 20 min after administration of each dose of halofantrine and the blood concentrations of halofantrine in samples obtained

---

0704550f5th jpg

Figure 5 The incidences of monomorphic ventricular tachycardia VT and torsade de pointes TdP Group n values are vehicle=5 clofilium=8 terfenadine=7 and halofantrine=6 P <0 05 compared to

---

1267547457 png

---

toxicity tbl1 jpg

with the control Table 1 Mean body weight changes and relative liver weight before and after treatment with halofantrine in Wistar rats The changes in the mean value of serum bilirubin and serum hepatospecific markers in all the groups are shown in table 2 There was a significant increase in the levels of total and

---

0703470f8th jpg

Figure 8 Effect of halofantrine on HERG channel inactivation a Time course of recovery from inactivation was obtained by a single exponential fit to the initial hook elicited by the steps to

---

0703823f4th jpg

Figure 4 The concentrations of halofantrine measured by high performance liquid chromatography in blood samples taken 20 min after administration of each dose of halofantrine from animals receiving

---

0703470f6th jpg

Figure 6 Envelope of tails protocol for HERG channels Representative current traces from a cell under control conditions a and 300 nM halofantrine b using the protocol as shown c Relative

---

0703470f1th jpg

Figure 1 HERG channel blockade by halofantrine Currents were elicited before a and after 300 nM halofantrine b using the potocol shown Depolarizing steps 3 9 s in duration were applied from

---

0703470f5th jpg

Figure 5 Effect of halofantrine on HERG current during prolonged depolarization a Representative current traces control and after 300 nM halofantrine generated by a 40 s depolarizing step to +10

---

medicine jpg

and treatment antimalarial drug Hoffman LaRoche LTD helped us with the final development and New Drug Application NDA submission to the FDA Halofantrine This treatment antimalarial drug was discovered and initially developed at the Division of Experimental Therapeutics WRAIR

---

fig10n gif

Compared with mefloquine + artesunate coartemether caused less nausea vomiting and dizziness Fig 10 Figure 10 Nausea vomiting and dizziness with coartemether or mefloquine + artesunate The relative risk of developing nausea with mefloquine + artesunate versus

---

african DANFAN gif

---

0703470f7th jpg

Figure 7 Effect of halofantrine on activation and deactivation time constants Single exponential functions were fitted to activating currents generated as in Figure 1 to yield activation time

---