Re: proving non-bacterial mediated antiinflammatory effects

[Guest guest]

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> :

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> Can you show me your math for the conversion of 18 uM to milligrams,

> please and thankyou.

>

> Barb

>

300 Da is an average molecular weight for an abx. Things like

macrolides and rif are heavier, chloramphenicol lighter. Doxy is 444

Da, per wikipedia. The biggest molecule that will penetrate a typical

gram-negative bug, at least under classical in vitro conditions, is

around 600 Da.

For a drug of molecular weight 300 (in Daltons, Da), 1 uM = 0.3 ug /mL.

1 mol denotes an absolute amount: 6.02 * 10^23 molecules. This weighs

X grams for a molecule of X Da. Therefore 1 mol of doxy weighs 444 g.

1 M deonotes a concentration: 1 mol /liter.

1 uM denotes 10^-6 mol /liter.

Now multiply [10^-6 mol /liter] by [444 g /mol of doxy]:

444 * 10^-6 g /liter is the result.

Thats 444 ug /liter, or 0.444 ug /mL.

So 18 uM doxy is 18 * 0.444 = 8 ug /mL.

Now, I must say the Cmax achieved by doxy is higher than I remember.

This paper says ~4 ug /mL for a 200 mg dose.

http://www.pubmedcentral.gov/picrender.fcgi?artid=352008 & blobtype=pdf

Thats the one-dose Cmax and the steady-state Cmax will be a bit higher

as the drug (having a half life around 16 hours) builds up over

multi-day dosing. I think the steady-state Cmax should be around 8 ug

/mL for daily 200 mg dosing.

So we should see a steady state Cmax around 8 * [40 mg / 200 mg] = 1.6

ug /mL for the 40 mg /d dose. Is that close enough to the measured

IC50 for neutrophil proteinases that inhibition of the latter could

make sense as an explanation here? I am not sure one way or the other.

Remember it will be lower than the Cmax most of the day (should be

around 1.0 ug /mL on average).