From: Stockis Armel <*Armel.Stockis*>

Date: Tue, 13 Jan 2009 21:02:31 +0100

David,

For children, simply parameterize as de-normalized CLcr = =

(Schwartz)*BSA/1.73

Of course you need an appropriate pediatric BSA formula, of which there =

are many.

----- Original Message -----

From: owner-nmusers

To: nmusers

Sent: Tue Jan 13 18:18:27 2009

Subject: [NMusers] Further questions about weight/CrCL correlations

*I'm very interested in comments from the group, since these issues are

very confused in the literature.

Schwartz equation:* CrCl (ml/min/1.73m2)= [length (cm) x k] / =

Scr

(Patient population: infants over 1 week old through adolescence (18

years old)) k = 0.45 for infants 1 to 52 weeks old

k = 0.55 for children 1 to 13 years old

k = 0.55 for adolescent females 13-18 years old

k = 0.7 for adolescent males 13-18 years old

When one uses this equation or others like, the CrCL is normalized to

body weight, and I agree that this is a good way to report an average

for a study population; however if you want to report the renal function =

for an individual, I think that you need to get rid of the normalization

e.g. BSA = 0.5 m^2 ; CrCL = 70 ml/min/1.73 m^2, then

Renal function (CrCL) for the individual would be 20 ml/min

Likewise if CrCL were a covariate for NONMEM, you would want to have the =

value for the individual.

If CrCL were 70 ml/min/1.73 m^2 for two individuals; one with 1.5 m^2

and another 2.0 m^2, I don't consider these indviduals as having the

same renal function. The covariate values would be 60.7 and 80.9

ml/min, respectively.

-------------------------------------------------------------------------=

----------------------------

Another separate issue:

If estimated creatinine clearance is determined by an equation, eg:

CrCL = (140-age)/scr x WT/72 ...

WT is already considered in the equation and you would expect a

correlation between the value for CrCL and WT.

Normalizing the value of CrCL does not seem like a good solution for the =

reason stated above.

The CrCL equation is really attempting to measure expected creatinine

production and then determine CL based on

Xu (0-t)/(sCr x t) with the assumptions that 100% creatinine

produced is excreted and sCr is constant.

Creainine production is related to body weight and theoretically

to lean body weight and muscle mass.

If the population were diverse in terms of age and sex, then the CrCL

values obtain may not correlate strongly with weight.

If a high correlation is observed between CrCL and WT, then would it be

possible to factor weight out

CrCL = (140-age)/scr would be the covariate, but then in the function

for clearance, add *weight/72 anywhere CrCL is used.

The covariate values would no longer correlate, but the same

relationship would be present.

I don't know if this would avoid the statistical problem of covariate

correlation or not.

--------------------------------------------------------

UCB Pharma S.A.

AllĂ©e de la Recherche, 60 1070 Brussels, Belgium

Tel: +32.2.559.99.99 - Fax: +32.2.559.92.10

Registration number : RPM/RPR Brussels 0403.096.168

VAT BE 0403.096.168 - Bank 210-0045962-36

--------------------------------------------------------

Legal Notice: This electronic mail and its attachments are intended =

solely for the person(s) to whom they are addressed and contain =

information which is confidential or otherwise protected from =

disclosure, except for the purpose for which they are intended. =

Dissemination, distribution, or reproduction by anyone other than the =

intended recipients is prohibited and may be illegal. If you are not an =

intended recipient, please immediately inform the sender and return the =

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Received on Tue Jan 13 2009 - 15:02:31 EST

Date: Tue, 13 Jan 2009 21:02:31 +0100

David,

For children, simply parameterize as de-normalized CLcr = =

(Schwartz)*BSA/1.73

Of course you need an appropriate pediatric BSA formula, of which there =

are many.

----- Original Message -----

From: owner-nmusers

To: nmusers

Sent: Tue Jan 13 18:18:27 2009

Subject: [NMusers] Further questions about weight/CrCL correlations

*I'm very interested in comments from the group, since these issues are

very confused in the literature.

Schwartz equation:* CrCl (ml/min/1.73m2)= [length (cm) x k] / =

Scr

(Patient population: infants over 1 week old through adolescence (18

years old)) k = 0.45 for infants 1 to 52 weeks old

k = 0.55 for children 1 to 13 years old

k = 0.55 for adolescent females 13-18 years old

k = 0.7 for adolescent males 13-18 years old

When one uses this equation or others like, the CrCL is normalized to

body weight, and I agree that this is a good way to report an average

for a study population; however if you want to report the renal function =

for an individual, I think that you need to get rid of the normalization

e.g. BSA = 0.5 m^2 ; CrCL = 70 ml/min/1.73 m^2, then

Renal function (CrCL) for the individual would be 20 ml/min

Likewise if CrCL were a covariate for NONMEM, you would want to have the =

value for the individual.

If CrCL were 70 ml/min/1.73 m^2 for two individuals; one with 1.5 m^2

and another 2.0 m^2, I don't consider these indviduals as having the

same renal function. The covariate values would be 60.7 and 80.9

ml/min, respectively.

-------------------------------------------------------------------------=

----------------------------

Another separate issue:

If estimated creatinine clearance is determined by an equation, eg:

CrCL = (140-age)/scr x WT/72 ...

WT is already considered in the equation and you would expect a

correlation between the value for CrCL and WT.

Normalizing the value of CrCL does not seem like a good solution for the =

reason stated above.

The CrCL equation is really attempting to measure expected creatinine

production and then determine CL based on

Xu (0-t)/(sCr x t) with the assumptions that 100% creatinine

produced is excreted and sCr is constant.

Creainine production is related to body weight and theoretically

to lean body weight and muscle mass.

If the population were diverse in terms of age and sex, then the CrCL

values obtain may not correlate strongly with weight.

If a high correlation is observed between CrCL and WT, then would it be

possible to factor weight out

CrCL = (140-age)/scr would be the covariate, but then in the function

for clearance, add *weight/72 anywhere CrCL is used.

The covariate values would no longer correlate, but the same

relationship would be present.

I don't know if this would avoid the statistical problem of covariate

correlation or not.

--------------------------------------------------------

UCB Pharma S.A.

AllĂ©e de la Recherche, 60 1070 Brussels, Belgium

Tel: +32.2.559.99.99 - Fax: +32.2.559.92.10

Registration number : RPM/RPR Brussels 0403.096.168

VAT BE 0403.096.168 - Bank 210-0045962-36

--------------------------------------------------------

Legal Notice: This electronic mail and its attachments are intended =

solely for the person(s) to whom they are addressed and contain =

information which is confidential or otherwise protected from =

disclosure, except for the purpose for which they are intended. =

Dissemination, distribution, or reproduction by anyone other than the =

intended recipients is prohibited and may be illegal. If you are not an =

intended recipient, please immediately inform the sender and return the =

electronic mail and its attachments and destroy any copies which may be =

in your possession. UCB screens electronic mails for viruses but does =

not warrant that this electronic mail is free of any viruses. UCB =

accepts no liability for any damage caused by any virus transmitted by =

this electronic mail. (Ref: #*UBP1208)

--------------------------------------------------------

Received on Tue Jan 13 2009 - 15:02:31 EST