World Health Organization (WHO) estimated in 2016 there were 216 million case of malaria around the world, and 14,6 million happens in South East Asia. Recurrence is still a problem in vivax malaria eradication program, it happens because the activation of hypnozoite, the dormant state of malaria parasite inside the liver. The only antihypnozoite available in the market is primaquine with the dose recommended my Ministry of Health 15 mg/day for 14 days.
These days, primaquine is the only drug to prevent recurrence. Therapeutic success rate is influenced by many factors including pharmacokinetic, pharmacodynamics, and CYP2D6 gene copy variation. CYP2D6 gene determine the activity of enzyme CYP2D6, the enzyme in the liver that turns primaquine into its active form.
Drug pharmacokinetic plays a huge role in optimal dose determination. Pharmacokinetic study in vivax malaria patient is needed to determine the dose and therapy success. Most primaquin pharmacokinetic data is obtained from healthy subjects, and it didn’t describe the real use of primaquine in real life. Therefore, a study on pharmacokinetic and pharmacodynamics of primaquine is needed to analyze the influence of CYP2D6 to primaquine effectivity in adult male vivax malaria patient.
A researcher from Medical Science Doctoral Program FMUI, dr Anggi Gayatri, SpFK did the research, and divided it into two parts. The first part is analyzing pharmacokinetic and pharmacodynamics od primaquine as an anti-recurrence drug. And the second part is analyzing the influence of CYP2D6 gene copy variation with recurrence of malaria.
The result shows that the use of piperaquine or pironaridine along with primaquine can increase the level of primaquine in the circulation. However, the increase of primaquine is not accompanied by increase of effectivity. Other than that, the increase of gene CYP2D6 man decrease recurrence risk, so it can be included that genetic characteristic of CYP2D6 is a factor that determines primaquine therapy success.
This study also shows that there’s no optimal level of primaquine found in the body to make it act as anti-recurrence. Therefore, optimal dose primaquine cannot be counted, even though dose counting is very useful to lower the recurrence of malaria. It is recommended for other researcher to do a clinical trial comparing the effectivity and safety of low dose primaquine (15 mg/day) and high dose (30 mg/day).
The result was presented by dr. Anggi Gayatri, SpFK on her doctoral hearing on Wednesday May 8th 2019 in IMERI Auditorium. The dissertation was titled “Pharmacokinetic/Pharmacodynamic Model of Primaquine Population and Analysis of Genetic Factor Enzyme CYP2D6 Analysis to Vivax Malaria Recurrence”.
Acted as the head examiner was Prof. Dr. dr. Suhendro, SpPD-KPTI. And other examiner included Prof. Dr. dr. Inge Sutanto, M.Phil, SpParK; dr. Instiaty, SpFK, PhD; Prof. Dr. Yahdiana Harahap, MS, Apt from Faculty of Pharmacy University of Indonesia; Farah N. Coutrier, PhD from Molecular Biology Institution of Eijkman; and Prof. dr. Rovina Ruslami, SpPD, PhD from Padjajaran University.
At the end of the hearing, Prof. Dr. dr. Ari Fahrial Syam, SpPD-KGEH, MMB as the head of the hearing inaugurated dr. Anggi Gayarti, SpFK as a Doctor in Medical Science of FMUI. Through their closing remarks, promotor Prof. Dr. dr. Rianto Setiabudy, SpFK and co-promotors Prof. Dr. dr. Purwantyastuti, MSc, SpFK and Prof. Kevin Baird, PhD hoped this research can be considered when giving primaquine to prevent vivax malaria.
(Public Relations FMUI)