Atazanavir

PD Dialyzability: Unlikely

Pharmacokinetic Parameters [1] [2] [3]

  Atazanavir
Molecular Weight (Da) 704
Plasma Protein Binding (%) 86
Volume of Distribution (L/Kg) 88 L (Based on weight of 69-70 kg. Vd = 1.27 L/kg (calculated))
Hepatic Metabolism Extensive hepatic metabolism (CYP3A4)
Excreted Unchanged (%) 7
Half-Life; Normal Renal Function (hours) 7
Half-Life; ESRD (hours) Unknown

CAPD/CCPD Dosing:

No dosing recommendation for PD population found in literature, However, given extensive hepatic metabolism, it is unlikely that dosage adjustment is required. Consider therapeutic drug monitoring given high interpatient variability [4]. In HD patients, regardless of administration in relation to dialysis, atazanavir levels were 25-40% reduced in comparison to controls with normal renal function. However, only 2.1 % of the given dose was found to be cleared during HD [5].

Literature Summary:

Title Patient Intervention Outcome Note
Atazanavir: a novel inhibitor of HIV-protease in haemodialysis [6]
  • 48 year old African male undergoing HD diagnosed with severe acute renal failure secondary to nephropathy related to HIV.
  • Atazanavair 400 mg/day, lopinavir/ritonavir 532/132 mg/day, and efavirenz 60 mg/day x 2 weeks
  • In comparison to reference range, atazanavir AUC elevated when administered concurrently with efavirenz and ritonavir
  • No adverse effects observed.

References

[1]Foisy M, Tseng A, Marr T. Selected properties of atazanavir. Immunodeficiency Clinic [Internet]. 2015 Jan [cited 2018 Jan 14]. 1-11. Available from: www.hivclinic.ca
[2]Wishart DS, Knox C, Guo AC, Shrivastava S, Hassanali M, Stothard P, et al. Drugbank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res. 2006 Jan 1;34(Database issue):D668-672.
[3]Colombo S, Buclin T, Cavassini M, Décosterd LA, Telenti A, Biollaz J, et al. Population pharmacokinetics of atazanavir in patients with human immunodeficiency virus infection. Antimicrob Agents Chemother,2006;50(11):3801-8.
[4]Higgins N, Tseng A, Sheehan NL, la Porte CJL. Antiretroviral Therapeutic Drug Moniotring in Canada: Current Status and Recommendations for Clinical Practice. Can J Hosp Pharm 2009;62(6):500-509.
[5]Agarwala S, Eley T, Child M, Wang Y, Persson A, Filomoro D, et al. Pharmacokinetics of atazanavir in severely renally impaired subjects including those on hemodialysis [abstract 2]. 8th International Workshop On Clinical Pharmacology of HIV Therapy. Budapest, Hungary, April 16-18, 2007.
[6]Izzedine H, Launay-Vacher V, Peytavin G, Valantin MA, Deray G. Atazanvir: a novel inhibitor of HIV protease in haemodialysis. Nephrol Dial Transplant 2005;20(4):852-853.