Title: Paul R
I would like to identify maximal concentrations in tissue,
corresponding time of Cmax tissue, and time and AUC of these
concentrations above a target concentration (eg, MIC for antibiotics or
1 uM for taxol). I identified the Cmax and associated Tmax in
simulated data for 'tissue' in the following code adapted from earlier
posts 99jul292004.html
. It works, but in the output table I am then required to
extract the Cmax and Tmax as the maximum values in the $TABLE (eg MAX()
in EXCEL, accomplishing little with the NONMEM code), or manually as
the last value in columns 'Cmax' and 'Tmax' before the null values
begin.
So to my questions:
1) How can the singular Cmax value identified by the last non-null
value in my IF statement be captured (apparently the "read-out" that
Prof Sheiner referred to in his comments on Cmax in earlier threads)
with its corresponding Tmax value and saved, for example, in a file
such as 'patab1'?
2) In a somewhat related fashion, has anyone code they can suggest to:
a) Start and stop the elapsed time for which concentrations are
above an MIC or other specified concentration (or effect)
b) Store previous time and concentration values so that the AUC
during this time above MIC can be calculated using trapezoid or
log-trapezoid methods?
Many thanks, as always.
Paul
$SUBROUTINES ADVAN6 TOL=7
$MODEL
COMP=(CENTRAL DEFDOSE DEFOBS)
COMP=(TISSUE)
$PK
CL=THETA(1)*WGT*EXP(ETA(1)); CL
V1=THETA(2)*WGT*EXP(ETA(2)); VPARENT
Q= THETA(3)*WGT; Q
V2=THETA(4)*WGT; V2
K10=CL/V1
K12=Q/V1
K21=Q/V2
S1=V1
$DES
D1=-A(1)*(K10+K12)+A(2)*K21
DADT(1)=D1
D2=A(1)*K12 - A(2)*K21
DADT(2)=D2
IF (D2.GT.0) THEN
CMax= A(2)/V2
TMax= TIME
ELSE
CMax=0
TMax=0
ENDIF
$TABLE ID TIME AMT RATE BOLT WGT CNC1 CNC2 Y1 Y2 CMaX TMaX NOPRINT
ONEHEADER
--
Paul R.
Hutson, Pharm.D.
Associate
Professor
UW School
of Pharmacy
777
Highland Avenue
Madison
WI 53705-2222
Tel 608.263.2496
Fax
608.265.5421
Pager
608.265.7000, p7856
Cmax, Tmax, and Time and AUC above threshold such as MIC
This should work:
IF(TIME.EQ.0) THEN
CMAX=0
TMAX=0
ENDIF
CC = A(2)/V2
IF(CC.GT.CMAX) THEN
CMAX= CC
TMAX= T
ENDIF
MIC=1
RT=0
IF(CC.GT.MIC) RT=1
DADT(3)=RT ; time above threshold
DADT(4)=RT*CC ; AUC when CC > MIC
$ERROR
CC2=A(2)/V2
CC7=A(7)
CC8=A(8)
$TABLE ID TIME CMAX TMAX CC2 CC7 CC8
The last record of each patient should provide desired values.
Leonid
--------------------------------------
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web: www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
tel: (301) 767 5566
Paul Hutson wrote:
> I would like to identify maximal concentrations in tissue, corresponding time of Cmax tissue, and time and AUC of these concentrations above a target concentration (eg, MIC for antibiotics or 1 uM for taxol). I identified the Cmax and associated Tmax in simulated data for 'tissue' in the following code adapted from earlier posts /99jul292004.html < http://www.cognigencorp.com/nonmem/nm/99jul292004.html >/ . It works, but in the output table I am then required to extract the Cmax and Tmax as the maximum values in the $TABLE (eg MAX() in EXCEL, accomplishing little with the NONMEM code), or manually as the last value in columns 'Cmax' and 'Tmax' before the null values begin.
>
> So to my questions:
>
> 1) How can the singular Cmax value identified by the last non-null value in my IF statement be captured (apparently the "read-out" that Prof Sheiner referred to in his comments on Cmax in earlier threads) with its corresponding Tmax value and saved, for example, in a file such as 'patab1'?
>
> 2) In a somewhat related fashion, has anyone code they can suggest to:
>
> a) Start and stop the elapsed time for which concentrations are above an MIC or other specified concentration (or effect) b) Store previous time and concentration values so that the AUC during this time above MIC can be calculated using trapezoid or log-trapezoid methods?
>
> Many thanks, as always.
> Paul
>
> $SUBROUTINES ADVAN6 TOL=7
> $MODEL
> COMP=(CENTRAL DEFDOSE DEFOBS)
> COMP=(TISSUE)
>
> $PK
> CL=THETA(1)*WGT*EXP(ETA(1)); CL
> V1=THETA(2)*WGT*EXP(ETA(2)); VPARENT
> Q= THETA(3)*WGT; Q
> V2=THETA(4)*WGT; V2
> K10=CL/V1
> K12=Q/V1
> K21=Q/V2
>
> S1=V1
>
> $DES
> D1=-A(1)*(K10+K12)+A(2)*K21
> DADT(1)=D1
> D2=A(1)*K12 - A(2)*K21
> DADT(2)=D2
> IF (D2.GT.0) THEN
> CMax= A(2)/V2
> TMax= TIME
> ELSE
> CMax=0
> TMax=0
> ENDIF
>
> $TABLE ID TIME AMT RATE BOLT WGT CNC1 CNC2 Y1 Y2 CMaX TMaX NOPRINT ONEHEADER
> --
>
> Paul R. Hutson, Pharm.D.
>
> Associate Professor
>
> UW School of Pharmacy
>
> 777 Highland Avenue
>
> Madison WI 53705-2222
>
> Tel 608.263.2496
>
> Fax 608.265.5421
>
> Pager 608.265.7000, p7856