Malaria N° 2 - Subject N° 11

EFFICACY OF QUINIDINE VERSUS QUININE TO TREAT MALARIA IN KENYA
A.J. Oloo, W.M. Watkins, W. Ekissa & al.

SUMMARY
We conducted a randomized clinical trial to compare the efficacy of Quinidine Vs Quinine to treat Plasmodium falciparum malaria in Western Kenya between 1989-1991.
A total of 200 patients with uncomplicated malaria were treated with oral Quinine or Quinidine at a dose of 10 mg salt per kg body weight, every 8 hours for 7 days (maximum 600 mg per dose). The 7 days follow-up was completed by 93 patients (Quinine) and 96 (Quinidine). We monitored clinical, parasitological biochemical and ECG changes.
The two groups were comparable with respect to age, weight, clinical status and parasite density, thus confirming randomization was effective. Mean parasite clearance times were 59.1 + 15.2 and 59.4 + 15.6 hrs for Quinine and Quinidine respectively (p = 0.90). Fever clearance times were similar 36.0 + 16.8 and 38.4 + 16.8 hrs for Quinine and Quinidine (p = 0.39). No hypoglycaemic episode (Blood glucose < 2.2 mmol/L) were recorded in either group, although 4 subjects on Quinine had blood glucose in the range of 2.2 - 2.5 mmol/L during the treatment period. The ECG changes for Quinine and Quinidine were comparable although there were slightly more QTc change (> 25 % of baseline) among the Quinidine group. The difference was not statistically significant. No patient had QTc prolongations > 50 % of the baseline.
All ten isolates tested in-vitro against Quinine and Quinidine were inhibited at concentrations < 256 pmol/well. No growth was observed beyond this value which is consistent with borderline sensitivity.
The pharmacokinetics of Quinidine gave Tmax of 2.5 (0.9) hrs and elimination t/2 of 10.2 (2.5) hrs. For Quinine Tmax was 2.3 (0.6) hrs and t/2 of 12.4 (2.3) hrs. Cmax for Quinidine was 2.9 (0.8) mg/1 and for Quinine 10.2 (4.3) mg/1. These values are consistent with those already obtained elsewhere.
This investigation confirms the equipotent efficacy of Quinidine and Quinine to treat malaria in Kenya. We cannot extrapolate these findings to severe and complicated malaria when there may be differences in bioavailability and safety profiles. Continued moniroring of their efficacy, especially for Quinine, in severe malaria is now a priority area for research.