alexa A One-compartment Constant Rate Intravascular Infusion
ISSN: 2470-6965

Malaria Control & Elimination
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Research Article

A One-compartment Constant Rate Intravascular Infusion Model for the Evaluation of Increases in Hematocrit after Artemisinin-based Combination Treatments of Acute Falciparum Malaria in Children

Akintunde Sowunmi1,2*, Kazeem Akano1, Adejumoke I Ayede3, Godwin Ntadom4, Temitope Aderoyeje2, Elsie O Adewoye5 and Bayo Fatunmbi6

1Department of Pharmacology & Therapeutics and Institute for Medical Research & Training, Nigeria

2Department of Clinical Pharmacology, University College Hospital, Ibadan, Nigeria

3Department of Paediatrics, University of Ibadan, Ibadan, Nigeria

4National Malaria Elimination Programme, Federal Ministry of Health, Abuja, Nigeria

5Department of Physiology, University of Ibadan, Ibadan, Nigeria

6World Health Organization, Regional Office for the Western Pacific, Cambodia

*Corresponding Author:
Akintunde Sowunmi
Department of Clinical Pharmacology
University College Hospital, Ibadan, Nigeria
Tel: +2348023359390
Email: [email protected]

Received Date: October 26, 2015 Accepted Date: November 19, 2015 Published Date: November 26, 2015

Citation: Sowunmi A, Akano K, Ayede AI, Ntadom G, Aderoyeje T, et al. (2015) A One-compartment Constant Rate Intravascular Infusion Model for the Evaluation of Increases in Hematocrit after Artemisinin-based Combination Treatments of Acute Falciparum Malaria in Children. Malar Cont Elimination S1:S1-006. doi: 10.4172/2470-6965.1000S1-006

Copyright: © 2015 Sowunmi A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

 

Abstract

Increases in hematocrit frequently follow successful treatment of uncomplicated falciparum infections in children, but there is no pharmacokinetic model for the analyses of the increases in hematocrit following artemisinin-based combination treatments (ACTs) in malarious children. A one-compartment constant rate intravascular infusion model (CRIVIM), which employed the principles of constant rate intravenous infusion of drugs (CRIVID), was used to evaluate the kinetics of the increases in hematocrit after artesunate-amodiaquine (AA) or artemether-lumefantrine (AL) treatments in 112 malarious children. The model assumed baseline hematocrit was zero, a constant rate increase in hematocrit from baseline following treatment, and it involved semi-logarithm plots of the difference between hematocrit at plateau and that at earlier times, against the corresponding times. Hematocrit reached a plateau in a median time of 28 days after treatment started. Mean plateau hematocrit was 6.7% (95%CI 5.9.-7.5) and was similar in AA- and AL- treated children [6.8% (95%CI 6-7.7), n = 81 v 6.3% (95%CI 4.9-7.7), n = 31, P = 0.56]. Times to plateau were significantly shorter and plateau hematocrit significantly lower in non-anemic compared to anemic children. Overall, declines from semi-logarithmic plots were monoexponential with mean half-time of hematocrit of 2.5 days (95%CI 2.2-2.8). Half-times were similar in AA and AL-treated children [2.4 days (95%CI 2.1-2.8) v 2.7 days (95%CI 2-3.3), P = 0.46], and were significantly shorter in anemic compared to non-anemic children [2.1 days (95%CI 1.8-2.4, n = 57) v 2.9 days (95%CI 2.4-3.5, n = 55), P = 0.01). Mean anemia recovery time was 13.8 days (95%CI 11.9 – 15.7). Bland-Altman analysis of 7 or 8 multiples of anaemia half-time and anaemia recovery times showed narrow limit of agreement with insignificant biases (P = 0.17 or 0.68, respectively). Steady state parameters were independent of baseline parasitemias. The one-compartment CRIVIM permits evaluation of increases in hematocrit following ACTs and may be used in observational and clinical studies in uncomplicated falciparum malaria.

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