Determinants of darunavir cerebrospinal fluid concentrations: impact of once-daily dosing and pharmacogenetics

AIDS
Andrea CalcagnoStefano Bonora

Abstract

To compare cerebrospinal fluid (CSF) darunavir and ritonavir concentrations in patients receiving darunavir/ritonavir 800/100 mg once daily or 600/100 mg twice daily. To determine the influence of single-nucleotide polymorphisms in the genes encoding for blood-brain barrier transporters (ABCB1 3435 C>T, ABCB1 1236 C>T, ABCB1 2677 G>T, SLCO1A2 38 A>G, SLCO1A2 516 A>C, ABCC2 -24 G>A) on darunavir and ritonavir penetration into CSF. Comparative pharmacokinetics study in patients. Plasma and CSF darunavir and ritonavir concentrations (2-26 h after drug intake) were determined by a validated HPLC coupled with mass spectrometry method in adults on darunavir-based combination antiretroviral therapy undergoing a lumbar puncture. HIV-infected patients on once-daily darunavir/ritonavir had significantly lower CSF darunavir trough concentrations and CSF-to-plasma ratios than patients on darunavir/ritonavir twice-daily (10.7 versus 38.2 ng/ml and 0.32 versus 0.90%; P < 0.05). No significant effect of single-nucleotide polymorphisms in the genes encoding for blood-brain barrier transporters was noted apart from slightly higher CSF darunavir penetration in patients carrying OATP1A2 uncommon variants. This is the first study to compare daruna...Continue Reading

References

Oct 30, 2007·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Antonio D'AvolioGiovanni Di Perri
Mar 27, 2009·AIDS Research and Human Retroviruses·Aylin YilmazMagnus Gisslén

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Citations

Nov 20, 2012·CNS Drugs·Christine EisfeldIngo Husstedt
May 14, 2014·The Journal of Antimicrobial Chemotherapy·M Arab-AlameddineUNKNOWN Swiss HIV Cohort Study
Jun 22, 2014·The Journal of Antimicrobial Chemotherapy·Thomas N KakudaRichard M W Hoetelmans
Apr 3, 2014·Journal of Clinical Pharmacology·Cecile A DelilleIghovwerha Ofotokun
Apr 11, 2015·Current HIV/AIDS Reports·Francesca FerrettiRichard W Price
Oct 5, 2014·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Andrea CalcagnoStefano Bonora
Jul 15, 2016·Expert Opinion on Investigational Drugs·Narasimha M MiddeSantosh Kumar
Jun 19, 2018·Expert Opinion on Pharmacotherapy·Vincenzo SpagnuoloAdriano Lazzarin
Sep 10, 2014·Clinical Pharmacokinetics·Andrea CalcagnoStefano Bonora
Jun 3, 2017·The Journal of Antimicrobial Chemotherapy·Hanni BartelsCatia Marzolini
Apr 27, 2013·Molecular Pharmaceutics·Catia MarzoliniAnna Seelig

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