The increasing resistance of P. falciparum strains to the current antimalarial drugs
makes the searching of new drugs an urgent task. The compound Ro 42-1611 is an
antimalarial drug that arises from a chinese herb Artabotrys uncinatus. Since its
synthesis, Ro 42-1611 was used in three different clinical trials to treat falciparum
malaria in Africa, but how it works in the South America malaria patients is obscure.
Althouh being an effective antimalarial, a proper therapeutic dose to achieve the
supressive cure of falciparum malaria has not been established yet. The purpose of
this study is to evaluate the tolerance, the toxicity and the efficacy of 3 different dose
schedules of Ro 42-1611 in the treatment of falciparum malaria. It was an open,
prospective and randomized trial carried out in Maraba/Para State in male patients
with maximum 80 kg bodyweight. All patients had fever or another constitutional
malaria symptom and had a positive thick blood smear to P. falciparum (≥ 200 and ≤
50,000 parasites/mm³). In a hospital, they were assigned into 3 groups according to
drug administration time: Group I - 1,500 mg twice a day for 24 hours; Group II -
1,500 mg twice a day for 48 hours and Group III - 1,500 mg twice a day for 72 hours.
Before treatment, the following procedures were recorded from all patients: personal
data, height and weight, malarial signs and symptoms, history of simultaneous drug
intake, body temperature, vital functions (respiratory rate, blood pressure), parasite
count, haematology and blood chemistry assesments and electrocardiogram. Ouring
the treatment, all those parameters were followed, including adverse reactions to Ro
42-1611. Statistical analysis (Friedman variance test) were performed on laboratory
tests results. Sixteen patients were enrolled in the study: 5 patients in Group I; 6 in
Group II and 5 patients in Group III. Among patients, age ranged from 17 to 41 years
old (mean 266). body weight from 44 to 72 kg (mean 54.9). The assexual parasite
count ranged from 200 to 40,000 parasites/mm³
. Regarding those variables, there
were homogeneity in 3 groups. According to the protocol, clinical and laboratory data
were evaluated, with the following results: the minimum and the maximum fever
clearence time was 9 to 48 hours respectively. The mean assexual parasite
clearence was 53.6 hours, without any statistical significance among the groups
(p=0.7264). There were statistical significative difference (p=0.0046) in the
hematocrit values before treatment (00), and the third (02) and the eighth (07) day
of the follow-up. It was observed an increase in the leukocyte count between 02 and
07, also of statistical significance (p=0.0171), as well in the platelets of 00 and
07/02 and 07 (p=0.0001). Between DO and 07, statistical significative reduction
ocurred in the values of total bilirrubin (p=0.0024), alkaline phosphatase (p=0.0195)
and urea (p=0.0168). There were no statistical significative difference nor in the
evalution of electrocardiogram results neither in the blood pressure. Short adverse
reactions were mild to moderate. In the end of the treatment, 87,5% of patients were
completely free of parasites, but just 2 achieved a radical cure (12,5%), both
included in Group III. Any of the schedule treatment showed efficacy. Perhaps such
efficacy might be attained using Ro 42-1611 in a superior dose, for a longer period
of time or in association with other antimalarial in further studies.
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