Maximizing Gabapentin bioavailability.

[Jamshyd]

As many here know, Gabapentin is a very uneconomical drug. Even as generic, it costs a shit-load of money, and as most of you know it has horrible and fluctuating oral bioavailability.

From what I gather, it has absolutely no use taken rectally because it is a Zwitteron, or something like that. I have no idea but both I and pubmed can confirm the fact that gabapentin cannot be taken rectally.

I assume the zwitteron thingy applies to nasal absorption.

Short of injection (which I'd do if I had less talc anc cellulose to deal with), I'd like to collect as much info as possible about increasing oral bioavailability.

Literature search was not very helpful. The only thing I gathered is that frequent divided dosing is better than taking it all at once.

---

Does anyone know which is better, an acidic or an alkaline gut pH for the absorption of gabapentin?

What foods should one avoid, what foods should one eat, is it better before, after, or between meals? (literature seems to suggest that during meals is the best).

Are there any supplements one can take to improve its absorption?

Thanks a lot in advance...

 

[nuke]

I've done a crazy amount of experimenting and I've found the following is best:
Take 150mg at a time. Stagger the doses by 45 minute interval. Take with a snack each time.

That usually would get me just plastered on 600mg, but I would need to have no tolerance and it takes about 2 hours after the first one to feel anything. My experience has been that the effects are variable among individuals and that tolerance occurs incredibly fast.

 

[Jamshyd]

Oh for sure, I have an ungodly tolerance to it because I use it medicinally. My doses are in the grams.

I will follow your method in 300mg increments (that's basically 1 cap), and see what happens).

 

[MurphyClox]

Yo Jamshyd, your question was already researched. Take for example these 2 abstracts:

"Inter- and intra-subject variability in gabapentin absorption and absolute bioavailability."
Epilepsy Research 2000, 40(2-3), pp.123-127

Abstract
Gabapentin (GBP) is a non-metabolized, non-plasma protein bound, renally excreted antiepileptic drug that is actively absorbed via the system L amino acid transporter. Previous studies have demonstrated that gabapentin displays dose-dependent absorption.
Objectives: These studies were conducted to det. inter- and intra-subject variability of gabapentin absorption. Two prospective clin. studies in healthy adult volunteers were conducted. Coeff. of variation (CV) was used to express variability of gabapentin absorption.
Methods: Study A: 400-mg single dose, randomized, cross-over study to assess bioavailability of four different gabapentin formulations (9 males, 11 females; mean age and wt. 41 yr, 75.1 kg). Plasma was serially collected up to 48 h and bioavailability (F) calcd. post-dose to det. concn.-time curves (AUC). All four formulations were bioequiv., thus repeated measures anal. was performed to assess inter-and intra-subject variability. Study B: 600-mg single dose study (15 males, 35 females; mean age and wt. 31.1 yr, 72.7 kg) was conducted to det. inter-subject variability in gabapentin F. Urine was collected over 48 h and bioavailability (F) calcd. Urine and plasma gabapentin concns. were measured by HPLC-UV.
Results: Study A: Overall mean (CV) of GBP AUC values was 34.124 .mu.g/h per mL. Inter-subject CV for AUC was 22.5% and intra-subject CV was 12.1%. Study B: Overall mean (SD) GBP F was 49.313.6%. Inter-subject CV of F was 27.6%.
Discussion: The inter-subject variability in gabapentin absorption is substantially less than that of the inter-subject variability. This indicates that one would expect a wide range in gabapentin absorption between subjects; however, a much smaller variability within a subject. The within subject variability of gabapentin is small enough that plasma drug monitoring may be used to assess gabapentin absorption for a given subject and the benefit of dose individualization.

"Gabapentin bioavailability: effect of dose and frequency of administration in adult patients with epilepsy."
Epilepsy Research 1998, 31(2), pp.91-99

Abstract
Gabapentin (GBP) is a non-metabolized antiepileptic drug that is eliminated by renal excretion and displays saturable, dose dependent absorption. The recommended dosing schedule for GBP is t.i.d. At large daily doses, oral bioavailability (F) may be improved by giving the daily dose more frequently. The objective is to evaluate whether switching GBP dosage regimen from t.i.d. to q.i.d. results in increased oral bioavailability. This study consisted of 2 parts; a computer simulated pharmacokinetic model and a clin. pharmacokinetic study in 9 adult epileptic patients receiving 3600 mg/day and 11 receiving 4800 mg/day. All patients were evaluated during both t.i.d. and q.i.d. regimens. F were detd. by calcn. of percent of dose excreted unchanged using steady-state 24-h urine collections and were compared using a paired t-test. At 3600 mg/day, mean F following t.i.d. and q.i.d. dosing were 38.7 and 40.0%, resp. At 4800 mg/day, mean F following t.i.d. and q.i.d. dosing were 29.2 and 35.6%, resp. Good agreement was obsd. between values from this study and predicted values based on the pharmacokinetic model. Improved GBP F at doses of 3600 mg/day was not achieved with more frequent drug administration, and thus is not warranted. At 4800 mg/day, a 22% increase in F was obsd. with more frequent drug dosing. GBP F may be significantly increased by q.i.d. vs. t.i.d. dosing, depending upon dose level. This increase in F however must be balanced against the inconvenience of more frequent dosing. Therapeutic drug level monitoring may aid in the evaluation of such pharmacokinetic maneuvers.

(full articles available upon PM-request)

________________________________


Apart from this, you might be interested to read about XP13512 ("gabapentin enacarbil"). It's a gabapentin-prodrug that gets actively (!) transported by intestinal transporters.


Selected bibliography:

"XP13512 [(±)-1-([(α-isobutanoyloxyethoxy)carbonyl]aminomethyl)-1-cyclohexaneacetic acid], a novel gabapentin prodrug: I. Design, synthesis, enzymatic conversion to gabapentin, and transport by intestinal solute transporters."
Journal of Pharmacology and Experimental Therapeutics 2004, 311(1), pp.315-323

"XP13512 [(±)-1-([(α-isobutanoyloxyethoxy)carbonyl]aminomethyl)-1-cyclohexaneacetic acid], a novel gabapentin prodrug: II. Improved oral bioavailability, dose proportionality, and colonic absorption compared with gabapentin in rats and monkeys."
Journal of Pharmacology and Experimental Therapeutics 2004, 311(1), pp.324-333

"Clinical pharmacokinetics of XP13512, a novel transported prodrug of gabapentin."
Journal of Clinical Pharmacology 2008, 48(12), pp.1378-1388

(other publications are available, including numerous patents)

Cheers, Mr. Murphy

 

[Thou]

First off that you for that information Murphy I've been scanning the web for the last few days looking. I just now encountered this thread.

Oh for sure, I have an ungodly tolerance to it because I use it medicinally. My doses are in the grams.

I will follow your method in 300mg increments (that's basically 1 cap), and see what happens).

If you don't mind my asking, what is your daily dose Jam?

I've just started taking gabapentin again in increments of 400 mg three times per day and already I'm noticing the therapeutic values I had experienced the first week waning considerably.

I'd personally like to go up to 2400 mg daily although instead of 800 T.I.D. I wanted to try 400 6 times a day or a similar dosing schedule to that effect.

I too am interested whether stomach PH plays a role in absorption so if anyone has the answer I'd be delighted to hear it.

Thanks

 

[MurphyClox]

First off that you for that information Murphy I've been scanning the web for the last few days looking. I just now encountered this thread.

At least somebody noticed my last post

 

[RedLeader]

I've done a crazy amount of experimenting and I've found the following is best:
Take 150mg at a time. Stagger the doses by 45 minute interval. Take with a snack each time.

That usually would get me just plastered on 600mg

I have been taking gabapentin for 6 months now, but I have always dosed all at once. I have tried some large doses (2400mg usually) and it was nice, but not great.

I just now have started with the staggering method, and I very much agree with it. It's great!

I've been doing 300mg every 30 minutes for about 3 hours to get to a really nice place.

Again, I repeat, stagger gabapentin!!!

I might try 150mg every 20 minutes over 4-5 hours in a week or so and see how that compares. But doing what I described above knocked my socks off, and showed me a completely different side of this compound.

 

[nuke]

The problem is the amino acid transporter gets saturated so no more can be transported. I don't know what the exact time at which it ceases to be saturated by the drug, but I'm guessing it's around 45 minutes to an hour. The bioavailability is also slightly enhanced with food.

Gabapentin is weird in that the bioavailability goes down almost linearly with increasing dose -- so whether you're taking 150mg (about when it starts to decline) or 600mg, nearly the same amount of the drug is absorbed. This is because of the above mentioned transporter saturation. The rest gets excreted. Hence, the staggering method and lower doses.

 

[RedLeader]

^ Understood.

With that said, I'm going to instead try :45 increments tonight.

Thank you for your elaboration.

 

[RedLeader]

Okay, given the known similarities between gabapentin and pregabalin, would the staggering approach also work for pregabalin? Thoughts?

 

[barry351]

My thoughts on gabbapentin brand name neurontin,I have been a user of this for more than a year.I doubt many know this and it needs to get out there,and before I tell all I need to say to the one that said gabbapentin has no uses I dont agree at all it can for some be great for some types of nerve pain.I take it just because it puts me on a better level hard to explain.What I really would like to let people know is if one is in serious opiate withdrawal you must take way more than the maximum recommended dose which is 800 milligrams,I am supposed to take 800 mills 3 times a day thats the max dose.I was in opiate withdrawal and took 4 of my 800 milligram gabbapentin and thought wow relief. I was totally amazed,I thought man people need to know this,and then I thougt maybe its just me so when a friend came over asking for one of my 8 milligram buprenorphine and was to low to give one I said hey try these out,he took 4 800-s and was also amazed. This drug is easy to get from most doctors for they most I feel know little about it. I asked my psyciatrist for it told her I had tried it and it made me feel better so no problem, a friend also had no problem.Some doctors may ask you to start out on a low dose so give it time and just move up.I just told her I had taken the 800 mill rite off but she still gave me 300 then 600 then to 800 in about a month or 2 so I say give it a try especially if you are in and out of opiate withdrawal lots, which can get very old you already know if and opiate addict. Just one problem the drug is expensive as said above,I am on dshs and get many of my drugs paid for.dshs is very picky about what they pay for I had to get approved by whats called the pharmacy appl. board to be on neurontin it took a week and got it, they dont pay for my buprenorphine or my soma (carisoprodal) I am on klonipin 2 milligrams 4 times a day they pay for that. I was lucky to find a doctor to give me the klonipin and soma it may not last for long for he is 81. Hope this helps someone.Just in case some think oh he gets soma and klonipin thats what helped well I am an addict and take more than supposed to I was out of both my klonopin and soma and buprenorphine when I took the gabbapentin for withdrawal,later b351.

 

[nuke]

Okay, given the known similarities between gabapentin and pregabalin, would the staggering approach also work for pregabalin? Thoughts?

The pharmacokinetics for pregabalin are pretty regular if I remember right, it's just straight absorbed without metabolism and then excreted unchanged. So you can probably eat as much as you want whenever you want.

Absorption and Distribution

Following oral administration of LYRICA capsules under fasting conditions, peak plasma concentrations occur within 1.5 hours. Pregabalin oral bioavailability is ≥90% and is independent of dose. Following single- (25 to 300 mg) and multiple-dose (75 to 900 mg/day) administration, maximum plasma concentrations (Cmax) and area under the plasma concentration-time curve (AUC) values increase linearly. Following repeated administration, steady state is achieved within 24 to 48 hours. Multiple-dose pharmacokinetics can be predicted from single-dose data.

The rate of pregabalin absorption is decreased when given with food, resulting in a decrease in Cmax of approximately 25% to 30% and an increase in Tmax to approximately 3 hours. However, administration of pregabalin with food has no clinically relevant effect on the total absorption of pregabalin. Therefore, pregabalin can be taken with or without food.

Pregabalin does not bind to plasma proteins. The apparent volume of distribution of pregabalin following oral administration is approximately 0.5 L/kg. Pregabalin is a substrate for system L transporter which is responsible for the transport of large amino acids across the blood brain barrier. Although there are no data in humans, pregabalin has been shown to cross the blood brain barrier in mice, rats, and monkeys. In addition, pregabalin has been shown to cross the placenta in rats and is present in the milk of lactating rats.

https://www.pfizerpro.com/product_info/lyrica_pi_clinical_pharmacology.jsp

 

[barry351]

I have just awoken this mourning and thought I would re-read this thread on gabbapentin and on doing so I realized that before posting I should read more carefully the posts by others before spewing my thoughts here.what I would like to add to my above last night 4 am to tired to be giving others info post is that jamshyd and nuke are very correct in that gabbapentin is way to expensive and does build tolerance very fast,in one week I dont get anywhere near the same affect as I did with the first dose,also I noticed that jamshyd said his doses are in the grams,this also made me realize that when I said the max dose was 800 milligrams 3 times a day that,that was the max dose here in the usa,other countries I should have known may have much different doseing amounts.I should also add that I read (sorry cant give exact site I read it on but it was a true study) gabbapentin when taken with a certain amount of morphine became 44% more available to you and this I believe from experience for I have done a gram of (we have shitty tar H here) heroin and the affect was not worth the price I paid,and a day later with same H and same amount but with having taken say 2 hours before 3 800 milligram gabbapentin tabs I awoke on the floor to my mom pissed off thinking I took klonipin and H again when in fact it was gabbbapentin and H. I was totally out of klonopin,so as with klonopin mixed with an opiate gabbapentin and an opiate must also have a synergistic effect,to those that dont know what a synertistic affect is it is like say 2+2 =6 . The methadone clinic which is 50 miles away (or I would be on it) wont even allow one to be takeing a benzodiazapine which the family of these drugs is to long to list but here are a few klonopin generic clonazapam,valium generic diazapam,xanex generic alprazolam,and many more lams and pams. So be very carefull when mixiing other drugs especially opiates and other downers,I have lost a few friends over this exact mixing of opiates and any other downers.

 

[RedLeader]

https://www.pfizerpro.com/product_info/lyrica_pi_clinical_pharmacology.jsp

Based on their "3 hours," I'd venture to say that it should be staggered a bit faster. A mat of mine will be trying this soon and I'll report back with results.

Edit: Putting my faith in pfizer's words = lol

 

[jeah]

so would me taking 1800mg earlier affect the stagger results if I did 600mg every hour from now on? usually I tak 1800, 1800 2 hour later and 1800 3-4 hours after that. would be nice to take 600mg at a time every hour.

just wondering about flooding receptors...

what is anyone's daily dose? mine is 2400mg so 4X600 tabs. i usually take twice that (4,800mg) every other day. it works for my sleep and restless leg syndrome very well. in helps my fiancee's pregnancy pains but she is only on 600X2 daily. very early in pregnancy. she got off klonopin and adderall.

It nevery really makes me drowsy it seems to be a cure all. and I probably only take that dose twice a week. it has strange effects at all dose levels but I have been on it for 6 months. I have also had a grand mal coming off of klonopin so I made the switch from klonopin to neurontin. after a month long klonopin withdrawl (4mg for 5 years), anyway, off all things been prescribed many great things all the time neurontin is what I could not live witohut. I can't say enough about this drug it reallt woroks for me. I also have severe ADHD and hypomania but anyway, best medicine, psychoactive occasionally wonder drug that helps even everything out without any unintended side effects.. at least in normal 600-2400 q.i.d doses.

 

[The Ghost of Omar]

Just breaking my message cherry... Just moved up to 600mg 2x day but not sure what I'm supposed to notice.... Just like with all these frickin' antidepressant/non-benzo anti-anxiety meds they can be quite subtle - and for those of us (not moi naturally) who have trained the brain for the more instant relief chemicals it's fucking hard to be patient with "regular" meds.

 

[Nexius]

Bringing back the past....

I'm practicing the stagger method right now, I always take lyrica but it's so unglodly expensive.

Thus, I went and got myself a script for gaba 180 x300mg

I took a single dose of 4.8grams knowing it wasnt going to do much...

I'm trying this stagger method right now, 600mg a hour (300mg x30 minutes)

I'll report back tonight


Takin the kids to the park for the whole dayyyyyyyyyyyyyyyyyyyyyyyy

Get some sunshine

Day 2 of opiate cold turkey

And I'm feelin grrrrrreeeeeaaaatttttttttttt

EDIT:

Yeah i really don't feel that great, but I feel better than one normally does during detox
Taking massive doses of protein, amino acids and vitamins are really working... I slept like a baby, with the aid of jwh
I woke up feeling refreshed
It's going to be a good day


I think I may be on to something here

 

[fryingsquirrel]

My usual recreational dose is 3600 mgs. My wifes is 12000 (OMFG). We'll definately try staggering doses. Naproxen (aleve) increases absorbtion 12-15%. Whether this is true at recreational dose levels is likely unresearched.

 

[drunken_etard]

I am prescribed it at 900mgs a day. I have taken doses up to 2100-2400mgs and did acheive any sort of high. Maybe a bit of fuzzyness in the head and a little bit off balance...But no real high.

But I find it can potentiate some drugs.

 

[SizzleSword]

I doubt this has anything to do with bioavailability, but I've always noticed that caffeinated soda seems to 'bring on' the effects of gabapentin, especially with staggered doses. I usually dose 900mg with a soda, another 900mg twenty five minutes later, and finally a 1200mg dose with more soda an hour and fifteen minutes after the first dose. I'm usually feeling all the effects at +02:30 (sociability, reduced anxiety, shiny surfaces, slight floating sensation, very slight closed-eye imagery) and they usually last for the rest of the day more or less.

When I first started using gabapentin, I would dose around 3000mg at once but I found out that it was a big waste after I started trying the staggered doses. Tolerance builds strong and fast, and at one point I was having diminished effects even up to two weeks after my last dose, but that was still taking one large dose (3000mg or more) at once. Nowadays I'm usually taking gabapentin two to three times a week at up to 6000mg (1800mg, 1800mg twenty five minutes later, 2400mg an hour and fifteen minutes after first dose) using staggered doses and I'm not noticing the diminished effects at all unless I attempt dosing two days in a row.

So, yeah.. If anyone's getting upset about the tolerance issue, I'd definitely try staggered dosing because I can tell you from experience that works a heck of a lot better than taking one massive dose at once. Try some soda, too. Gabapentin's a lot better when you're able to take it when you want to, not just when you -think- it'll work. Peace.