I am not understanding the cytochrome p450 inhibition literature in the way that it is being used here. Analgesic effect requires metabolism, if you inhibit an opiate's metabolism why is this desirable, with the exception of use with norbuprenorphine? Just trying to understand why the grapefruit, pomelo, etc is used deliberately... is it broadly misunderstood?
Grapefruit juice or Pumelo, variously spelled, also Pomelo, etc.
SS37dOH is right, folks are generally trying to inhibit the enzymes that
break down the drug. That way the drug sometimes lingers longer in your system.
There are at least two drugs that
do require metabolism to get to a more potent metabolite, and those are codeine and tramadol. Codeine gets converted to morphine in your liver, and tramadol to nor-tramadol (desmethyl-tramadol), both requiring CYP2D6 (dihydrocodeine conversion to dihydromorphine does too, but the rate is negligible). You want to
avoid inhibiting CYP2D6 with these drugs.
Nor-buprenorphine isn't a drug, but a metabolite of buprenorphine, and it doesn't hardly enter your brain. That's an example of where you might want to inhibit the enzyme that converts buprenorphine to nor-buprenorphine, since the first has analgesic properties and the second doesn't.
A better example is with oxycodone. CYP3A4 converts it to nor-oxycodone, which is active but weak. Meanwhile, CYP2D6 converts it to the more potent oxymorphone/Numorphan. So inhibiting CYP3A4 leaves more for CYP2D6.
How much gain a person gets is questionable, since all of them get conjugated too, meaning your kidneys just piss out most of them.l
There are lots of different plant sources for enzyme inhibitors. Grapefruit juice is actually pretty messy and inhibits lots of liver enzymes. Better options are things like cimetidine, which are cleaner and shorter-acting in their inhibition.