- On 1 Dec 2000 at 10:52:21, "Dr. Federico Pea" (federico.pea.aaa.med.uniud.it) sent the message

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Dear all,

Does anybody know which is the defined daily dose for nimesulide?

Thank you in advance

--

Federico Pea, MD

Clinical Pharmacologist

Institute of Clinical Pharmacology & Toxicology

Medical School

University of Udine

P.le SM Misericordia, 3

33100 Udine

Italy

email: federico.pea.-a-.med.uniud.it

URL:http://www.uniud.it/ifct/welcome.html

Fax: +39 0432 559833 - On 2 Dec 2000 at 12:08:14, ml11439.-a-.goodnet.com sent the message

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Dr.Pea,

Avery's Drug Treatment 4th ed. lists the dose of the

analgesic/anti-inflammatory Nimesulide as being 100-200mg

twice a day.

Mike Leibold, PharmD, RPh

ML11439.at.goodnet.com - On 8 Dec 2000 at 13:40:52, ml11439.-a-.goodnet.com sent the message

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Dr. O'Connor,

The AUMC is used in noncompartmental pharmacokinetic analysis

of linear pharmacokinetic systems. The concept is derived from

statistical moment theory where the mean and variance of a radomn

variable are the first and second moments of the probability

density function. The probability density in the case

of AUMC is C(t)/AUC, and the first moment is the mean residence time

for the drug: MRT= AUMC/AUC. The second moment is the variance in the

MRT, analagous to the variance in the mean of randomn variable with

a continuous probability density function.

AUMC is actually the first moment of AUC, and is equal to

Integral(0->inf)tC dt. The AUMC is the area of the curve of a plot

of the "product" of the concentration and time versus time from

zero to infinity. The AUMC is derived from probability theory and

allows pharmacokinetic analysis of any linear model without the

need for compartmental analysis. This is since the concept is

embedded in probability and not in mechanistic pharmacokinetic

modeling.

The AUC is also called the zero moment of the blood level

versus time curve. The statistical probability density is

C(t)/AUC, and this is the probability density function of

statistical moment theory.

The equation for clearance involving AUC is also considered

model independent, applicable to any linear pharmacokinetic

system:

Cl= D(iv)/AUC

The C(t)/AUC term being the probability density function of

statistical moment theory, is basically arguing that the probability

of observing t during the distribution of the drug is:

p(t) = C(t)/AUC

The integral of the probability density function is the

probability distribution function, and it represents the

probability of oberving t over a specified interval:

p(t<=T)= integral(0->T) C(t)/AUC

MRT or the mean residence time is analagous to the mean of

a randomn variable t with a probability density function of

p(t) as above. The C(t)/AUC probability density function

represents the fraction of AUC occurring at time t, and the sum

of the product of tC(t)/AUC over time gives the mean of t

observed during the drug plasma concentration curve.

MRT= integal(0->inf) tp(t)= integral(0->inf)tC(t)/AUC

Although noncomparmental pharmacokinetic has several

theoretical advantages, its clinical application is perhaps

less clear than standard deterministic or Bayesian pharmacokinetic

analysis. This is since adequate clinical predictability can

be obained with the later with only a few plasma levels, and

the variance observed seems to be more a problem of changes in

organ clearance.

Mike Leibold, PharmD, RPh

ML11439.-at-.goodnet.com

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