Grapefruit Juice and Benzodiazepines?
I've heard conflicting things about the body's absorption of benzodiazepines when mixed near grapefruit juice. I've heard that grapefruit juice increases and decrease absorption - which is true? Please reference a source if possible.
Answers:
INCREASES.
http://www.pharmacists.ca/content/hcp/Re...
http://www.pharmgkb.org/do/serve?objId=1...
Grapefruit juice is a moderate inhibitor of the cyp3a4 isoenzyme in the P450 system, the same gutter that most benzodiazepines are substrates. This leads to higher serum levels for longer period of time because it causes a reduction in the metabolism rate of these drugs.
There doesn't seem to be to be any difference in absorption or bio-availability however. Just the duration and serum levels. Higher level or lower metabolism depending on how the effect is stated.
Grapefruit liquid has an effect on certain complexes in the liver (and other places, but for the purposes of this discussion let's stick to the liver) call cytochrome p450. These are responsible for metabolizing a lot of different drugs, including benzodiazepines. Grapefruit juice contains some compounds that are also processed by the cytochrome p450s.
So it's not so much that it changes the digestion as that it increases what we call the "bioavailability"--the active form of the drug is around for longer because the complexes that metabolize the drug are tied up with the compounds from the grapefruit liquid. The problem arises when you take your next dose of the benzodiazepine, which is prescribed on the assumption that you will have cleared the previous dose. Now you still enjoy some left in your system because the cytochrome p450 hasn't yet taken effort of it, and you take the new dose, and eventually you can reach an overdose stratum.
There are other things that can jump-start the process instead of slowing it down, so that may be where the confusion over increase/decrease comes in. They are called any inhibitors or inducers depending on what they do. (This is all highly over-simplified, you understand.)
Here's a table of the a variety of inhibitors/inducers. http://medicine.iupui.edu/flockhart/tabl...
For a longer (and possibly more cogent) explanation of the process, you might try here, but I warn you, it gets complicated fast: http://www.uky.edu/Pharmacy/ps/porter/CP...
Hope that help!
Related Questions:
How long does it help yourself to for Chloroform to dissipate through your body?
like... just if enough is given to put you to sleep for a surgery or what not. how long would it purloin approximately for it to leave your system? Chloroform isn't used these days in modern nonspecific anesthesia. The agents presently used are much safer and better. ...
Are doctors allowed to prescribe medication for themselves?? or their children/spouse?
It's been awhile since I worked in retail, but I believe the law is as follows. A physician can not write a prescription for themselves for drugs surrounded by Schedules II, III and IV. They can not write prescriptions for family for drugs in Schedules II and III.
Answers:
INCREASES.
http://www.pharmacists.ca/content/hcp/Re...
http://www.pharmgkb.org/do/serve?objId=1...
Grapefruit juice is a moderate inhibitor of the cyp3a4 isoenzyme in the P450 system, the same gutter that most benzodiazepines are substrates. This leads to higher serum levels for longer period of time because it causes a reduction in the metabolism rate of these drugs.
There doesn't seem to be to be any difference in absorption or bio-availability however. Just the duration and serum levels. Higher level or lower metabolism depending on how the effect is stated.
Grapefruit liquid has an effect on certain complexes in the liver (and other places, but for the purposes of this discussion let's stick to the liver) call cytochrome p450. These are responsible for metabolizing a lot of different drugs, including benzodiazepines. Grapefruit juice contains some compounds that are also processed by the cytochrome p450s.
So it's not so much that it changes the digestion as that it increases what we call the "bioavailability"--the active form of the drug is around for longer because the complexes that metabolize the drug are tied up with the compounds from the grapefruit liquid. The problem arises when you take your next dose of the benzodiazepine, which is prescribed on the assumption that you will have cleared the previous dose. Now you still enjoy some left in your system because the cytochrome p450 hasn't yet taken effort of it, and you take the new dose, and eventually you can reach an overdose stratum.
There are other things that can jump-start the process instead of slowing it down, so that may be where the confusion over increase/decrease comes in. They are called any inhibitors or inducers depending on what they do. (This is all highly over-simplified, you understand.)
Here's a table of the a variety of inhibitors/inducers. http://medicine.iupui.edu/flockhart/tabl...
For a longer (and possibly more cogent) explanation of the process, you might try here, but I warn you, it gets complicated fast: http://www.uky.edu/Pharmacy/ps/porter/CP...
Hope that help!
Related Questions:
How long does it help yourself to for Chloroform to dissipate through your body?
like... just if enough is given to put you to sleep for a surgery or what not. how long would it purloin approximately for it to leave your system? Chloroform isn't used these days in modern nonspecific anesthesia. The agents presently used are much safer and better. ...
Are doctors allowed to prescribe medication for themselves?? or their children/spouse?
It's been awhile since I worked in retail, but I believe the law is as follows. A physician can not write a prescription for themselves for drugs surrounded by Schedules II, III and IV. They can not write prescriptions for family for drugs in Schedules II and III.