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Deconstructing a Full Prescribing Information: Part VIII Friday 2/3/12

Posted by smcgamer in Deconstucting The.
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sigh…

Just now I realized I have more than four Deconstructing a Full Prescribing Information.  So I went over the same data twice in Part Five.  Oh well.

Onward nonetheless!

Insomnia again

Insomnia again (Photo credit: Foodie In Disguise)

Chronic Insomnia

The effectiveness of LUNESTA was established in five controlled studies in chronic insomnia.  Three controlled studies were in adult subjects, and two controlled studies were in elderly subjects with chronic insomnia.

Ah, chronic insomnia.  Guaranteed to waste thousands of hours a year!®©all rights reserved

Adults

In the first study, adults with chronic insomnia (n=308) were evaluated in a double-blind parallel-group trial of 6 weeks’  duration comparing LUNESTA 2 mg and 3 mg with placebo.

The (n=308) seems to mean that the group contained 308 adults with chronic insomnia.  If they each miss 4 hours of sleep per night, that’s 1 month 20 days of lost sleep per night!

Ahem… right.  Anyway, a double-blind study is a study in which neither the doctors or the patient know that they’re taking Lunesta.  This is to offset the placebo effect – where thinking about feeling better actually makes you feel better.  A parallel-group study is where two separate groups get two different medicines.

Objective endpoints were measured for 4 weeks.

From what I can find, an objective endpoint seems to be about tracking the results after going off of a medicine.

Both 2 mg and 3 mg were superior to placebo on LPS at 4 weeks.  The 3 mg dose was superior to placebo on WASO.

Ball-and-stick model of the (S)-zopiclone (esz...

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Placebo, as mentioned above, is a pill that does nothing.  But the patient who doesn’t know he’s getting placebo thinks it’s working, and feels better for it.  As for LPS, the only thing I could find was lipopolysaccharide, and I doubt that’s correct.  WASO seems to mean wake after sleep onset – waking up in the middle of the night.

So Lunesta beats placebo, and 3 milligrams of it stops you from waking up at night, at least better than placebo would.

In the second study, adults with chronic insomnia (n=788) were evaluated using subjective measures in a double-blind, parallel-group study comparing the safety and efficacy of LUNESTA 3 mg with placebo administered nightly for 6 months.  LUNESTA was superior to placebo on subjective measures of sleep latency, total sleep time, and WASO.

This time, 788 adults were studied.  Subjectivity is the opposite of objectiveness – it’s where a person lets their emotions and opinions show a little more than objectivity – where facts and truth matter.  Efficacy is the ability for something to produce an effect – in this case, aiding sleep.  Sleep latency is how long it takes one to get to sleep after going to bed.

So LUNESTA was shown to work better than placebo in getting to sleep, staying asleep, and being asleep for long enough to feel rested.

So that’s it for tonight.  I still can’t believe I repeated part five.  Oh well.  See you next time.

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Deconstructing a Full Prescribing Information : Part V Monday 1/30/12

Posted by smcgamer in Deconstucting The.
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If by tomorrow, I meant 382 days, then yeah, I meant tomorrow.  At any rate, we’re back for more Lunesta!

Pharmacokinetics Continued

Metabolism

Following oral administration, eszopiclone is extensively metabolized by oxidation and demethylation.

Ribbon diagram of human cytochrome P450 isozym...

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Once Lunesta is consumed, it’s metabolized (used) through oxidation and demethylation (which is removing methyl groups from a molecule).

The primary plasma metabolites are (S)-zopiclone-N-oxide and (S)-N-desmethyl zopiclone; the latter binds to GABA receptors with substantially lower potency than eszopiclone, and the former compound shows no significant binding to this receptor.

A metabolite is the intermediate or product of a metabolism (usage, so to speak).  Zopiclone is, to put it simply, a different type of eszopiclone that’s sold in Canada and the UK, and serves similar purposes to eszopiclone, zopiclone’s active stereoisomer.  A GABA receptor responds to gamma-aminobutyric acid, a neurotransmitter.  As we recall from an earlier post, a GABA receptor also helps with sleep, and blocking it hinders sleep (perhaps so Lunesta can do its job without the body getting in the way).

In vitro studies have shown that CYP3A4 and CYP2E1enzymes are involved in the metabolism of eszopiclone.

An in vitro study is a study with organic chemicals done outside of said chemical’s natural environment (like in a test tube).  Cytochrome P450 3A4 is one of the most important enzymes in xenobiotics, and Cytochrome P450 2E1 is also helpful in xenobiotics.  These studies have shown that these two enzymes help out in metabolizing Lunesta.

Eszopiclone did not show any inhibitory potential on CYP450, 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4 in cryopreserved human hepatocytes.

So Lunesta doesn’t harm or affect negatively any of those eight cytochrome enyzmes, which is probably a good thing.  Cryopreservation is keeping organic tissue really, really cold so it doesn’t spoil or rot.  A hepatocyte is a liver cell.  They create and store proteins, process waste, transforms carbohydrates and produces bile, cholesterol, and phosopholipids.