Kaletra drug metabolism?

[gregftl]

does anyone know which enzymes metabolize the drug kaletra?  is it CYP2D6?

[penguin]

Kaletra, metabolized in the liver by cytochrome P450 (CYP3A isoform).

for the purposes of drug interactions, other stuff metabolized by the same pathway (but not CYP2D6) should be avoided. prescribing info has full details.

hope that helps - kate

[Jacques]

Sorry to contredict you Penguin, but Ritonavir in the Kaletra formula is metabolized bye both CYP3a (CYP P450) and CYP2D6. Lopinavir however  is extensively and almost exclusively metabolized by CYP3A isoenzime. kaletra should then be seen as a potent inhibitor of CYP3A4 and , at a lesser degree, CYP2D6.

for more info:

http://www.hivtools.com/PI.php


Jacques

[penguin]

true, LPV/RTV can also inhibit CYP2D6 in vitro - as i understand it though, this don't happen at clinically relevant concentrations..?

kate

[newt]

All PIs have major involvement with P450s for metabloism. The primary P450s are 3A4 and 5 and there is some contribution to metabolism by the 2C sub-family and by 2D6. The majority of protease inhibitor metabolism occurs in the small intestine and liver. 70% of the P450 that you find in the small intestine is CYP 3A and the liver contains multiple P450s.  85% +/- of lopinavir (the biggie PI in Kaletra) follows this pattern. CYP 3A is not the only thng that's affected, though. Lopinavir can increase the activity of CYP 2C9 and 19, and ritonavir can induce the activity of CYP 1A2 and the 2Cs.

- matt

[Jacques]

Matt ,
Reading what you posted, do you think  ritonavir could interfere with meds that are also metabolized by Cyp2D6 ?  such as tricyclic agents (nortriptyline, amitriptyline).
I am asking this because I have been prescibed amitriptyline along with Norvir boosted Reyataz.  I am affraid that amitriptilyne might be boosted as well.

Jacques

[newt]

Jacques..

Yes, but not necessarily significant, it depends on you. Ritonavir may increase amitriptyline levels by 1.5-3 times.

But also decrease some meds eg noratriptyline. Or increase it.  Different studies got different results with nora...

This page has a handy table of interactions with anxiety meds etc

The Summary of Product Characteristics for ritonavir says:

"Ritonavir dosed as an antiretroviral agent is likely to inhibit CYP2D6 and as a result is expected to increase concentrations of amitriptyline. Careful monitoring of therapeutic and adverse effects is recommended when this medicine is concomitantly administered with antiretroviral doses of ritonavir." (Norvir Summary of Product Characteristics, Abbott Laboratories Ltd, February 2007)

The question is, does using ritonavir to boost another PI count as "dosed as an antiretroviral agent"? and the answer in many cases is probably no, and no dose adjustment to amitriptyline will be necessary, but for some people the answer may be yes, and a decrease in the tricyclic therefore needed.

This has to be managed as an empirical thing, if you get too much tranquility etc when using ritonavir and a tricyclic then perhaps take less of the anti-depressant.

- matt

[gregftl]

thank you guys...because i am taking 60mg. Cymbalta, 400mg Wellbutrin Sr. and 45mg of Dexedrine SR. daily and wanted to know if kaletra boosted these medications in the bloodstream

[Jacques]

Thank's Matt, this really helps me. In fact I am taking amitriptilyne  for unidentified leg pains and stiffness .(Or perhaps my doc believe they are caused by anxiety and want to calm me down a bit  ). The dosage is low (10 mg die) and he suggests to increase it to 25 mg die. So i guess that this will still be considered a low dose, even if Norvir increase it by three times.

thank you again,
bisous
Jacques
--------------------------------------------------------------------------------------------
Greg,
According to "check my meds" tool on this site , they are possible interactions between some of your meds. You should take a look as a first step. Click on the link below and follow instructions.

https://www.aidsmeds.com/cmm/index.php?action=AfterSearch

Jacques

[Bucko]

thank you guys...because i am taking 60mg. Cymbalta, 400mg Wellbutrin Sr. and 45mg of Dexedrine SR. daily and wanted to know if kaletra boosted these medications in the bloodstream

Greg-

I had some odd interactions with a variety of medications when I was on Kaletra, including Fentanol which I was using for chronic pain. I went right to the drug manufacturers (admittedly back in 2002-03) and they were unwilling or unable to give me straight answers.

No help here, but wanted to add a voice of support in your search for info.