Raltegravir

PD Dialyzability: Unlikely

Pharmacokinetic Parameters [1] [2]

  Raltegravir
Molecular Weight (Da) 444
Plasma Protein Binding (%) 83
Volume of Distribution (L/Kg) Unknown
Hepatic Metabolism UGT1A1
Excreted Unchanged (%) 9
Half-Life; Normal Renal Function (hours) 9
Half-Life; ESRD (hours) Unknown

CAPD/CCPD Dosing:

No studies were found in the PD population. Half-life of raltegravir was found to be slightly prolonged in patients with severe renal impairment (CrCl < 30 ml/min); however this was not clinically significant [3]. Given major hepatic metabolism, it is unlikely that dose adjustment is required for raltegravir in PD patients.

Literature Summary:

Title Patient Intervention Outcome Note
Pharmacokinetics of darunavir, etravirine, and raltegravir in an HIV-infected patient on haemodialysis. [4]
  • 49-year old HIV-positive virologically suppressed, male receiving HD 3x/week.
  • darunavir/ritonavir 600/100 mg twice daily, etravirine 200 mg twice daily, and raltegravir (morning dose given after HD)
  • In comparison to levels predialysis, raltegravir was found to be reduced by 82%.
  • Patient remained virally suppressed following one year of treatment.
  • Administration of raltegravir 400 mg supplemental dose pre-HD did not restore levels possibly due to intra- and inter-patient variability.
Minimal removal of raltegravir by hemodialysis in HIV-infected 1 patients with end stage renal disease. [5]
  • Patient 1: 53-year-old male diagnosed with HIV infection in 1984. Virologically suppressed (<50 copies/mL), CD-4 count 863 cell/mm^3. Receiving HD 3x/week.
  • Patient 2: 50-year-old man who was diagnosed with HIV infection in 1992. Virologically suppressed (<50 copies/mL), CD4+ count was 976 cells/mm^3. Receiving HD 3x/week.
  • nevirapine 200 mg twice daily and raltegravir 400 mg twice daily
  • efavirenz 600 mg once daily, tipranavir-ritonavir 500/200 mg twice daily, and raltegravir 400 mg twice daily.
Patient 1
  • hemodialysis extraction ratio: 5.5%
  • raltegravir hemodialysis clearance: 9.1 ml/min Patient 2
  • hemodialysis extraction ratio: 9.5%
  • raltegravir hemodialysis clearance: 19.1 ml/min
  

References

[1]Tseng A. Selected properties of Elvitegravir. Immunodeficiency Clinic [Internet]. 2015 Feb [cited 2018 Jan 19]. 1-6. 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]Iwamoto M, Hanley WD, Petry AS, Friedman EJ, Kost JT, Breidinger SA et al. Lack of a clinically important effect of moderate hepatic insufficiency and severe renal insufficiency on raltegravir pharmacokinetics. Antimicrob Agents Chemother 2009;53(5):1747-52.
[4]Giguere P, la Porte C, Zhang G, Cameron B. Pharmacokinetics of darunavir, etravirine, and raltegravir in an HIV infected patient on haemodialysis. AIDS 2009:23:740-2.
[5]Molto J, Sanz-Moreno J, Valle M, Cedeño S, Bonal J, Bouarich H et al. Minimal removal of raltegravir by hemodialysis in HIV-infected 1 patients with end stage renal disease. Antimicrob Agents Chemother 2010, epub ahead of print May 3rd.