microbial pharmacokinetics

[Guest guest]

On this subject I like H Nikaido's stuff best because it is

quantitative.

OK but just how quantitative is it - is it quantitative enough to

really make a difference? (Wooooooo, lil joke.) Well...

Apparantly the diffusion rates of drugs thru porins, and across/thru

the substance gram-negative outer membrane, can be pretty comparable.

At least, some heavily lipophilic substances enter (via membrane)

about as fast as some highly hydrophilic ones enter via porins. Things

may be different tho for molecules lying in between.

Bacteria have minute volume / surface area ratios. Consequentally, in

the absence of efflux or catabolism (beta-lactamases, etc), it takes

about 1 second for a drug to equilibriate into a typical gram-negative

bacterium (ie, for the drug concentration inside the bacterium to

reach the concentration present outside it). Pseudomonas aeruginosa

and some mycobacteria are however 100-1000x less permeable in general.

Nevertheless a drug theoretically equilibriates into them in about 5

minutes.

Thats why efflux (or beta-lactamases, etc) is really much more

fundamental to these organisms resistance; without it, their low

permeability would only afford them 5 extra minutes to smell the roses

before bacteriostasis/bactericide.