Hi again, Mark & Mark.
Ok, so most of my bookmarks on gabapentin were defunct or too specific and not about dosage considerations... so I had to go to google .... took me a bit.
AND, what turned up this time is little different than what I remember or perhaps found before. Not entirely surprising because every time I google this med something different comes up.
Anyway, I will post a few of the sources/articles.
1.
http://www.ncbi.nlm.nih.gov/pubmed/8022536
Quote:
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Plasma concentrations are essentially proportional to dosages up to 1,800 mg daily, which is the highest dosage used in double-blind, placebo-controlled clinical trials.
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2.
http://onlinelibrary.wiley.com/doi/1...01.02399.x/pdf
Quote:
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Peak plasma levels [...] are achieved 3±3.2 h after ingestion of a single 300-mg capsule [7, 10].
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Quote:
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As a result of the dose-dependent saturable absorption of gabapentin, C-max increases less than threefold when the dose is tripled from 300 to 900 mg [9]
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This tells us something a little more specific... not only the daily dose is significant, but the size of an individual dose is significant in absorption, becausee the transport mechanism (you can research this if you want) gets saturated... only a limited supply of "gabapentin taxi-cabs", lol. This suggests to me that taking a certain daily dosage split into a greater number of smaller doses can deliver slightly more gabapentin than taking fewer larger doses.
Quote:
Its extensive distribution is reflected in a volume of
distribution of ~0.6±0.8 L/kg [7, 9]. Cerebrospinal fluid (CSF) concentrations are 20% of plasma concentrations [11] and have been estimated at between 0.09 and 0.14mcg/ml [12]. Brain tissue concentrations are ~80% the plasma level [13]. In rats, the pancreatic and renal tissue concentrations were found to be eight and four times, respectively, higher than serum concentrations[11]. Pancreatic accumulation of the drug does not occur in humans as it exists in a highly ionised state at physiological pH and concentrations in adipose tissue are low [11].
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So, although it distributes outside the blood, it does not accumulate much in adipose tissue. This means weight is unlikely to have much impact on dosing considerations. (Perhaps a little, but would perhaps need more specifics on the albeit low concentration of drug in adipose tissue to believe that.)
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3.
http://www.rxmed.com/b.main/b2.pharm...NEURONTIN.html
Quote:
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Pharmacokinetics: Adults: Following oral administration of gabapentin, peak plasma concentrations are observed within 2 to 3 hours.
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3 hrs is faster than what I remember/stated... might have been "tainted" by my own experience.
Quote:
Absolute bioavailability of a 300 mg dose of Neurontin capsules is approximately 59%. At doses of 300 and 400 mg, gabapentin bioavailability is unchanged following multiple dose administration.
[...]
Plasma gabapentin concentrations are dose-proportional at doses of 300 to 400 mg q8h, ranging between 1 µg/mL and 10 µg/mL, but are less than dose-proportional above the clinical range (>600 mg q8h).
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300-400 mg q8h is 900 to 1200 mg a day -- plasma conc. is dose-proportional.
">600 mg q8h" would be more than 1800/day -- over 1800mg a da plasma conc. is less than dose-proportional.
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There is no correlation between plasma levels and efficacy.
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In other worsds, some people may respond with only a little in their blood, while others need a lot.
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4.
http://www.rxlist.com/neurontin-drug...armacology.htm
This source states something slightly different -- that availability decreases as the dose goes up, even starting at 900 mg/day. These numbers still show a progressive decrease in availability with increasing dose. I do find very interesting though that the
rate of decrease slows down as the dose goes up.
Quote:
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Gabapentin bioavailability is not dose proportional; i.e., as dose is increased, bioavailability decreases. Bioavailability of gabapentin is approximately 60%, 47%, 34%, 33%, and 27% following 900, 1200, 2400, 3600, and 4800 mg/day given in 3 divided doses, respectively. Food has only a slight effect on the rate and extent of absorption of gabapentin (14% increase in AUC and Cmax).
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waves