Influence of primaquine and ritonavir interaction on CYP3A4 mRNA expression in HepG2 cell culture

Adam Iskandarmudasyah, Melva Louisa, Arleni, Sri Widia Jusman, Franciscus D. Suyatna

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1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3-7
Number of pages5
JournalMedical Journal of Indonesia
Volume21
Issue number1
DOIs
Publication statusPublished - 1 Feb 2012

Keywords

  • CYP3A4
  • CYP450 induction
  • Drug interaction
  • Primaquine
  • Ritonavir

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