Raltegravir
============

**PD Dialyzability**: Unlikely

Pharmacokinetic Parameters [1]_ [2]_
--------------------------------------

======= ======
/////// |pk|
======= ======
|pk1|   |v1|
|pk2|   |v2|
|pk3|   |v3|
|pk4|   |v4|
|pk5|   |v5|
|pk6|   |v6|
|pk7|   |v7|
======= ====== 

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                |
+==========+============+================+==============+=====================+
| |L1|     | * |L2|     | * |L3|         | * |L4|       | * |L5|              |
| [4]_     |            |                | * |L6|       |                     |
+----------+------------+----------------+--------------+---------------------+
| |L7|     | * |L8|     | * |L9|         |   |L10|      |                     |
| [5]_     | * |L11|    | * |L12|        | * |L13|      |                     |
|          |            |                | * |L14|      |                     |
|          |            |                |   |L15|      |                     |
|          |            |                | * |L16|      |                     |
|          |            |                | * |L17|      |                     | 
+----------+------------+----------------+--------------+---------------------+ 

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. 

.. |pk| replace:: Raltegravir
.. |pk1| replace:: Molecular Weight (Da)  
.. |pk2| replace:: Plasma Protein Binding (%)
.. |pk3| replace:: Volume of Distribution (L/Kg) 
.. |pk4| replace:: Hepatic Metabolism 
.. |pk5| replace:: Excreted Unchanged (%) 
.. |pk6| replace:: Half-Life; Normal Renal Function (hours)
.. |pk7| replace:: Half-Life; ESRD (hours) 
.. |v1| replace:: 444
.. |v2| replace:: 83
.. |v3| replace:: Unknown
.. |v4| replace:: UGT1A1
.. |v5| replace:: 9
.. |v6| replace:: 9
.. |v7| replace:: Unknown
.. |L1| replace:: Pharmacokinetics of darunavir, etravirine, and raltegravir in an HIV-infected patient on haemodialysis. 
.. |L2| replace:: 49-year old HIV-positive virologically suppressed, male receiving HD 3x/week.
.. |L3| replace:: darunavir/ritonavir 600/100 mg twice daily, etravirine 200 mg twice daily, and raltegravir (morning dose given after HD)
.. |L4| replace:: In comparison to levels predialysis, raltegravir was found to be reduced by 82%. 
.. |L5| replace:: Administration of raltegravir 400 mg supplemental dose pre-HD did not restore levels possibly due to intra- and inter-patient variability.
.. |L6| replace:: Patient remained virally suppressed following one year of treatment.  
.. |L7| replace:: Minimal removal of raltegravir by hemodialysis in HIV-infected 1 patients with end stage renal disease. 
.. |L8| replace:: 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. 
.. |L9| replace:: nevirapine 200 mg twice daily and raltegravir 400 mg twice daily
.. |L10| replace:: Patient 1
.. |L11| replace:: 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.
.. |L12| replace:: efavirenz 600 mg once daily, tipranavir-ritonavir 500/200 mg twice daily, and raltegravir 400 mg twice daily.
.. |L13| replace:: hemodialysis extraction ratio: 5.5%
.. |L14| replace:: raltegravir hemodialysis clearance: 9.1 ml/min 
.. |L15| replace:: Patient 2
.. |L16| replace:: hemodialysis extraction ratio: 9.5%
.. |L17| replace:: raltegravir hemodialysis clearance: 19.1 ml/min