Home in the Clouds

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

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.

Image via Wikipedia

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.

Related articles

• Giant cell reveals metabolic secrets (physorg.com)
• GABA Signaling Prunes Back Copious ‘Provisional’ Synapses During Neural Circuit Assembly (medicalnewstoday.com)
• Study Of Genetic Regulation Of Metabolomic Biomarkers – Paths To Cardiovascular Diseases And Type 2 Diabetes (medicalnewstoday.com)
• GABA Signaling Prunes Back Copious Provisional Synapses During Neural Circuit Assembly (neurosciencenews.com)