- On 27 Oct 2003 at 17:47:29, =?ISO-8859-1?Q?Fr=E9d=E9ric_Lagarce?= (frederic.lagarce.-a-.st-serge.univ-angers.fr) sent the message

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The following message was posted to: PharmPK

Hi all,

I'm injecting a drug via the intrathecal route with an implanted

catheter. This device is then used to sample the CSF. 300 µl of CSF is

sampled for each time point (150 for the dead volume of the KT and 150

are kept for analysis). After analysis using LC/MSMS, I have the

profile of CSF drug concentration versus time. In log scale one can see

a distribution phase (rapid log linear decrease of the concentration in

the CSF, during the first 3 hours) after the decrease is slower and

linear. What PK parameters is it possible to calculate from this set of

data? I have performed a non compartmental analysis using kinetica. The

software calculate MRT and Thalf (I have chosen IV bolus model) is it

correct in that case?. The Vd given by the software is calculated from

the cmax, do I have to extrapolate a c0 from the elimination process

after initial distribution to calculate the apparent volume of

distribution in the intrathecal space? In parralel I have injected the

drug in plasma and calculated the PK parameters, but I don't know

precisely how to relate this parameters to the one I have calculated

for the intrathecal route.

if you have any litterature advice that i could use to solve this

problem please feel free to help me.

thanks very very much in advance to everyone who will take a few

minutes to help me.

Frederic lagarce - On 29 Oct 2003 at 11:44:55, "Prashant V Bodhe" (prashnvb.-a-.rediffmail.com) sent the message

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Dear Frederic lagarce

Using data one can do many calculations, programming. Ultimately what

is important whether these serve to you objectives or not.

Please tell us about your project objectives

DrPrashant - On 31 Oct 2003 at 12:40:12, "William Heijbroek" (william.heybroek.at.kinetics.demon.co.uk) sent the message

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Dear Frederic,

The common parameter here is thalf, as this measures the terminal

systemic

half-life which should be the same following any dose method.

You haven't described the drug and objectives but I guess you are

interested

in localised acute concentrations of drug. Cmax and AUC in the

intrathecal

space and maybe some dynamic measurements such as Emax and EC50 would

be of

interest.

Vd is usually calculated from clearance and elimination rate and would

be

different initially but following distribution should be similar for

the two

routes (Vz = Cl/kel). Clearance comes from expression, Cl = Dose/AUC.

The

AUC should be determined from plasma.

Hope this helps.

William Heijbroek

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