Pharmaceutical Equivalence of Some Commercial Samples of Artesunate and Amodiaquine Tablets Sold in Southwestern Nigeria

Purpose: To study the physical properties and dissolution profiles of commercial samples of artesunate and amodiaquine tablets. Methods: Fifteen generic brands of artesunate and five generic brands of amodiaquine tablets were obtained from drug retail outlets in Oyo and Ogun States in southwestern Nigeria. The tablets were subjected to various compendial tests including identification; weight uniformity; uniformity of content; content of active ingredient and uniformity of diameter. Additional tests used as a basis for the assessment of the pharmaceutical equivalence of the products include hardness; disintegration time and dissolution rate. Data obtained were analysed by correlation analysis; Chi-square and ANOVA. Results: Thirteen generic brands of artesunate (87) and four amodiaquine brands (80) investigated were imported. Two brands of the imported artesunate brands were found to contain undetectable amount of artesunate while another 8 samples contained overages. All the amodiaquine brands passed the assay test as stipulated by United States Pharmacopoeia (USP) for amodiaquine tablets while tablet disintegration time of amodiaquine products ranged from 5.8 - 20.7 min. All but one artesunate sample passed the disintegration test too. A majority of the artesunate brands tested had significantly different dissolution profiles (p 0.05). Four (80) of the amodiaquine tablet brands tested had similar dissolution profiles and percent drug released within 30 min (p 0.05). One amodiaquine brand demonstrated poor dissolution profile as it did not meet minimum dissolution requirements within 30 min. Conclusion: The detection of substandard artesunate tablets and a poorly formulated amodiaquine tablet amongst the few sample brands studied highlights the need for increased drug surveillance and monitoring of the qualities of antimalarial medicines currently in use in order to prevent widespread treatment failure

Histomorphologic Alterations of the Cerebellum of Wistar Rats following Amodiaquine Plus Artesunate Administration

Amodiaquine and artesunate are two antimalarial drugs sold in combination as Larimalr'. This drug is a very effective artemisinin-base combination. This study was to access the effects of amodiaquine and artesunate combination on the histology of the cerebellum. Twenty adult Wistar rats weighing between 150-180g were divided into four groups (A; B; C and D) of five animals each. Group A served as the control and the animals received distilled water; while group B received 8.75+2.86mg/kg of amodiaquine and artesunate combination for three days; group C received 8.75+2.86mg/kg of amodiaquine and artesunate combination for six days and group D received 17.50+5.71mg/kg of amodiaquine and artesunate combination for three days. Histological sections showed destruction of the Purkinje cortical layers in group B; with increased destructions in groups C and D compared to the control. These results reveal that amodiaquine and artesunate combination causes histological alterations; which were dose and time dependent and these may result in cerebellar dysfunction

Biological and Haematological Safety Profile of Oral Amodiaquine and Chloroquine in Healthy Volunteers with or without Plasmodium falciparum Infection in Northeast Tanzania

Amodiaquine (AQ); an effective antimalarial drug for uncomplicated malaria; has been greatly restricted after cases of life-threatening agranulocytosis and hepatic toxicity during prophylactic use. We conducted a hospital based open-label randomised clinical trial in 40 indigenous semi-immune healthy adult male volunteers with and without malaria parasites. The objective was to collect data on biological and haematological safety; tolerability; and parasitological efficacy to serve as baseline in the evaluation of the effectiveness of AQ preventive intermittent treatment against malaria morbidity in infants. Volunteers were stratified according to parasitaemia status and randomly assigned 20 participants each arm to three days treatment with either AQ or chloroquine (CQ). The level of difference of selected haematological and hepatological values pre-and post-trial were marginal and within the normal limits. Clinical adverse effects mostly mild and transient were noticed in 33.3CQ treated-aparasitaemic; 23.8of CQ treated-parasitaemic; 28.6of AQ-treated parasitaemic and 14.3of aparasitaemic receiving AQ. Amodiaquine attained 100parasitological clearance rate versus 70in CQ-treated volunteers. The findings indicate that there was no agranulocytosis or hepatic toxicity suggesting that AQ may pose no public health risk in its wide therapeutic dosage uses. Larger studies are needed to exclude rare adverse effects

Amodiaquine; sulfadoxine/pyrimethamine; and combination therapy for treatment of uncomplicated falciparum malaria in Kampala; Uganda:a randomised trial

Increasing Plasmodium falciparum resistance to chloroquine in sub-Saharan Africa necessitates use of alternative antimalarial agents. Affordable alternative treatments inlude sulfadoxine/pyrimethamine and amodiaquine. Combination of antimalarial agents can increase thepeutic resistance. We compared the efficacy of sulfadoxine/pryrimethamine; amodiaquine; and an amodiaquine/sulfadoxine/pyrimethamine combination for treatment of uncomplicated malaria in a region of high chloroquine resistance. Methods: Patients with symptoms of uncomplicated falciparum malaria and confirmed disease in Kampala; Uganda; were randomly assigned to receive sulfadoxine/pyrimethamine) plus placebo; amodiaquine (25mg/kg) sulfadoxine and 1.25mg/kg prymethamine) plus placebo; or amodiaquine plus sulfadoxine/pyrimethamine. Patients were followed up for 14 days; and clinical and parasitological outcomes were assessed. Findings: 90(400/445) of patients enrolled in the study successfully completed 14 days of follow-up. Treatment failure based on clinical criteria occurred in 13 of 131 (10) patients on sulfadoxine/pyrimethamine. Based on parasitological criteria; treatment failed in 26; 16; and 10of these patients; respectively. Amodiaquine/sulfadoxine/pyrimethamine was significantly more effective than sulfadoxine/pyrimethamine alone in children aged younger than 5 years (clinical failure in 3.5vs 13.9; respectively; risk difference 10.4[95CI; 1.6-19.3] p=0.021; parasitological failure in 12.8vs 26.4; risk difference 13.61.2-26.0] p=0.041) Interpretation Sulfadoxine/pyrimethamine; amodiaquine; and amodiaquine/sulfadoxine/pyrimethamine were all effective for treatment of uncomplicated falciparum malaria in Uganda. The amodiaquine/sulfadoxine/pyrimethamine combination was the most effective; and could be the optimum low-cost alternative to chloroquine in Africa

Etude comparative du traitement du paludisme non complique chez la femme enceinte en zone endemique (Chloroquine versus Amodiaquine)

Deux groupes de gestantes febriles infectees par Plasmodium ont recu respectivement la Chloroquine et l'Amodiaquine a la dose orale de 25mg/kg en 3 jours. Au 14eme jour; l'echec therapeutique est observe dans le groupe traite a la Chloroquine dans 5;7 pour cent des cas tandis que le succes therapeutique est total dans le groupe traite a l'Amodiaquine. Le prurit et le malaise sont les effets secondaires rencontres imputables a la prise des Amino-4-quinoleines