TY - JOUR
T1 - Influence of primaquine and ritonavir interaction on CYP3A4 mRNA expression in HepG2 cell culture
AU - Iskandarmudasyah, Adam
AU - Louisa, Melva
AU - Arleni, null
AU - Jusman, Sri Widia
AU - Suyatna, Franciscus D.
N1 - Publisher Copyright:
© 2012 Faculty of Medicine, Universitas Indonesia. All rights reserved.
PY - 2012/2
Y1 - 2012/2
N2 - Background: Concomitant treatment with antimalaria and antiretroviral drug is a new challenge in the management of malaria and HIV co-infection. Primaquine is a substrate and also an inhibitor of CYP3A4, while ritonavir is a substrate, an inhibitor, and also an inducer for CYP3A4. The objective of this study is to measure the CYP3A4 mRNA expression in HepG2 cell culture induced by primaquine and ritonavir co-treatment. Methods: For the initial study HepG2 cells were treated with 30, 40, 50 uM of primaquine; 2, 10, 20 uM ritonavir; DMSO ≤0.1% for negative control; or 20 uM rifampicin for positive control. While for the co-treatment study the cells were treated with 40 uM primaquine+10 uM ritonavir; DMSO ≤0.1%; or 20 uM rifampicin for 72 hours. The cells were harvested using trypsin-EDTA and total RNA was extracted using the Tripure isolation reagent. After determining the quantity of RNA spectrophotometrically, CYP3A4 mRNA expression was quantified using real-time reverse transcription polymerase chain reaction (RT-PCR). Results: The expression of CYP3A4 mRNA was up-regulated (1.22 fold over control) in HepG2 cells co-treated with primaquine and ritonavir. These data suggest that the induction effect of ritonavir was more dominant than the inhibitory effect of primaquine. Conclusion: Concomitant administration of primaquine and ritonavir result in up-regulation of CYP3A4 mRNA expression in vitro.
AB - Background: Concomitant treatment with antimalaria and antiretroviral drug is a new challenge in the management of malaria and HIV co-infection. Primaquine is a substrate and also an inhibitor of CYP3A4, while ritonavir is a substrate, an inhibitor, and also an inducer for CYP3A4. The objective of this study is to measure the CYP3A4 mRNA expression in HepG2 cell culture induced by primaquine and ritonavir co-treatment. Methods: For the initial study HepG2 cells were treated with 30, 40, 50 uM of primaquine; 2, 10, 20 uM ritonavir; DMSO ≤0.1% for negative control; or 20 uM rifampicin for positive control. While for the co-treatment study the cells were treated with 40 uM primaquine+10 uM ritonavir; DMSO ≤0.1%; or 20 uM rifampicin for 72 hours. The cells were harvested using trypsin-EDTA and total RNA was extracted using the Tripure isolation reagent. After determining the quantity of RNA spectrophotometrically, CYP3A4 mRNA expression was quantified using real-time reverse transcription polymerase chain reaction (RT-PCR). Results: The expression of CYP3A4 mRNA was up-regulated (1.22 fold over control) in HepG2 cells co-treated with primaquine and ritonavir. These data suggest that the induction effect of ritonavir was more dominant than the inhibitory effect of primaquine. Conclusion: Concomitant administration of primaquine and ritonavir result in up-regulation of CYP3A4 mRNA expression in vitro.
KW - CYP3A4
KW - CYP450 induction
KW - Drug interaction
KW - Primaquine
KW - Ritonavir
UR - http://www.scopus.com/inward/record.url?scp=85008881409&partnerID=8YFLogxK
U2 - 10.13181/mji.v21i1.471
DO - 10.13181/mji.v21i1.471
M3 - Article
AN - SCOPUS:85008881409
SN - 0853-1773
VL - 21
SP - 3
EP - 7
JO - Medical Journal of Indonesia
JF - Medical Journal of Indonesia
IS - 1
ER -