Effect of Artesunate on Disposition Profile of Amodiaquine in Amodiaquine-Artesunate Combination Formulated in Fixed or Separate Doses.
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J. Phann. Sci. & Pharm. Pract.
Background: The use of artemisinin combination therapies has been on the increase globally and most especially in sub-Saharan Africa since its adoption by WHO. Amodiaquine-artesunate combination has been accepted by most malarious countries and its efficacy and safety have been proven by studies reported in literature. However there is a dearth of publication regarding the possible effect of artesunate on the pharmacokinetics of amodiaquine. The objective of the study was to investigate the effect of interaction of artesunate on the systemic disposition of Amodiaquine in amodiaquine-artesunate formulation either in fixed or separate doses in healthy volunteers in Nigeria. Methods: Thirty healthy volunteers were enrolled in the study after informed consent. They were randomly divided into three groups (I, II, III) to products A, B and C respectively. The study adopted was a single dose, open, 3-way treatment and cross-over design with one month wash out period. Each volunteer in groups I and II was administered with amodiaquine 600mg and artesunate 200mg formulated in either fixed or separate doses while group III took amodiaquine 600mg only. Blood samples were taken for a period of 28days post drug administration. The pharmacokinetic parameters derived from the three formulations were analysed using analysis of variance (ANOVA). Results: The parametric estimates of pharmacokinetic data obtained from amodiaquine when given alone and in combination were compared. The maximum plasma concentration (Cm,,) was estimated as 0.69±0.23, 0.74±0.27 and 0.56±0.25 μg/ml; the plasma elimination half-life (t112) was 16.38±3.73, 19.51±6.38 and 18.41±7.24h whilst the area under plasma curve (AUC0_72") 258 was184.20±25.97, 185.01±31.52 and 186.35±30.16 ng.h/ml for products A, Band C respectively. Conclusion: With respect to comparative values, the results confirmed trends already observed in literature particularly regarding amodiaquine monotherapy. There was no significant difference amongst the three groups and within the two different formulations. We did not make any comparison with desethylamodiaquine-metabolite as it was not quantified but the chromatograms confirmed the existence of the major metabolite. .
ACT, Interaction , Amodiaquine-artesunate formulations , Pharmacokinetics , Amodiquine , Research Subject Categories::PHARMACY::Pharmaceutical chemistry
Akinleye M.O. Phillip I.M. Adepoju-Bello A.A. Coker H.A.B. (2014). Effect of Artesunate on Disposition Profile of Amodiaquine in Amodiaquine-Artesunate Combination Formulated in Fixed or Separate Doses