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Effects of MAO-A and CYP450 on primaquine metabolism in healthy volunteers

  • Treatment and Prophylaxis - Original Paper
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Abstract

Eliminating the Plasmodium vivax malaria parasite infection remains challenging. One of the main problems is its capacity to form hypnozoites that potentially lead to recurrent infections. At present, primaquine is the only drug used for the management of hypnozoites. However, the effects of primaquine may differ from one individual to another. The aim of this work is to determine new measures to reduce P. vivax recurrence, through primaquine metabolism and host genetics. A genetic study of MAO-A, CYP2D6, CYP1A2 and CYP2C19 and their roles in primaquine metabolism was undertaken of healthy volunteers (n = 53). The elimination rate constant (Ke) and the metabolite-to-parent drug concentration ratio (Cm/Cp) were obtained to assess primaquine metabolism. Allelic and genotypic analysis showed that polymorphisms MAO-A (rs6323, 891G>T), CYP2D6 (rs1065852, 100C>T) and CYP2C19 (rs4244285, 19154G>A) significantly influenced primaquine metabolism. CYP1A2 (rs762551, -163C>A) did not influence primaquine metabolism. In haplotypic analysis, significant differences in Ke (p = 0.00) and Cm/Cp (p = 0.05) were observed between individuals with polymorphisms, GG-MAO-A (891G>T), CT-CYP2D6 (100C>T) and GG-CYP2C19 (19154G>A), and individuals with polymorphisms, TT-MAO-A (891G>T), TT-CYP2D6 (100C>T) and AA-CYP2C19 (19154G>A), as well as polymorphisms, GG-MAO-A (891G>T), TT-CYP2D6 (100C>T) and GA-CYP2C19 (19154G>A). Thus, individuals with CYP2D6 polymorphisms had slower primaquine metabolism activity. The potential significance of genetic roles in primaquine metabolism and exploration of these might help to further optimise the management of P. vivax infection.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author upon reasonable request.

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Funding

This study was funded by the Ministry of Higher Education, Malaysia, under the Fundamental Research Grant Scheme [FRGS/1/2016/SKK09/UKM/02/1].

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Authors and Affiliations

  1. Faculty of Pharmacy, Jalan Raja Muda Abdul Aziz, Abdul Aziz, 50300, Kuala Lumpur, Malaysia

    Norliza Mat Ariffin, Farida Islahudin, Endang Kumolosasi & Mohd Makmor-Bakry

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  1. Norliza Mat Ariffin
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  2. Farida Islahudin
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  3. Endang Kumolosasi
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  4. Mohd Makmor-Bakry
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Correspondence to Farida Islahudin.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Section Editor: Ramaswamy Kalyanasundaram

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Ariffin, N.M., Islahudin, F., Kumolosasi, E. et al. Effects of MAO-A and CYP450 on primaquine metabolism in healthy volunteers. Parasitol Res 118, 1011–1018 (2019). https://doi.org/10.1007/s00436-019-06210-3

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  • DOI: https://doi.org/10.1007/s00436-019-06210-3

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