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From: Saeheum Song <ss.pkpdmodel_at_gmail.com>

Date: Sat, 6 Apr 2019 10:11:50 -0400

Generally speaking, the portion which undergoes saturatable clearance due

to ligand or receptor engagement will be negligible at high concentrations.

Therefore, it is recommend to use one saturable equation without needs of

dose dependent “IF .. THEN … ENDIF “ Statement

The followings are some programming comments in NONMEM coding.

IF(DOS.LT.200) THEN;; This assumes DOSE below 50 and 100 not 200

;;; LT = less than

;;; LE = less than or Equal to

TVKM = THETA (5)

TVVM = THETA (6)

;; THIS needs to be end in order to next if Then statement effective

*ENDIF;;*

;;;

TVKSS = 0

TVKINT = 0

TVKDEG = 0

TVRMAX = 0

IF(DOS.GT.100) THEN;;; This assumes that DOS 200 and 400

;;; GT = Greater than

;;; GE = Great or Equal to

TVKSS = THETA (7)

TVKKINT = THETA(8)

TVRMAX = THETA(9)

ENDIF

....

$DES

CONC=0.5*(A(1)/V1-RMAX-KSS)+0.5*SQRT((A(1)/V1-RMAX-KSS)**2+4*KSS*A(1)/V1)

;; CONC is simply A(1)/V1 and RMAX and KSS are undefined variables.

Hope it helps.

On Tue, Apr 23, 2019 at 8:49 AM Niurys.CS <amaranthfan_at_gmail.com> wrote:

*> Dear All,
*

*>
*

*> I'm working on the population pharmacokinetics of a mAb, in this study
*

*> 4 dose levels (50, 100, 200 and 400 mg) were evaluated. I tested
*

*> different models, but none of them fit well; that's why I decided to
*

*> find for each dose level the best model. I found the two lower dose
*

*> levels fitted to Michaelis Menten + CL linear model and the two higher
*

*> dose levels fitted to QSS Rtot model.
*

*> I think if I use this code, I'll find the best model for my data, so I
*

*> appreaciate your suggestions:
*

*>
*

*> $PK
*

*>
*

*> TVCL= THETA(1)
*

*> TVV1= THETA(2)
*

*> TVQ = THETA(3)
*

*> TVV2 = THETA (4)
*

*>
*

*> TVKM = 0
*

*> TVVM = 0
*

*>
*

*> IF(DOS.LT.200) THEN
*

*> TVKM = THETA (5)
*

*> TVVM = THETA (6)
*

*>
*

*> TVKSS = 0
*

*> TVKINT = 0
*

*> TVKDEG = 0
*

*> TVRMAX = 0
*

*>
*

*> IF(DOS.GT.100) THEN
*

*>
*

*> TVKSS = THETA (7)
*

*> TVKKINT = THETA(8)
*

*> TVRMAX = THETA(9)
*

*>
*

*> ENDIF
*

*>
*

*>
*

*> K = CL/V1
*

*> K12 = Q/V1
*

*> K21 = Q/V2
*

*> S1 = V1
*

*>
*

*> ;----------------------------------
*

*> $DES
*

*>
*

*> CONC=0.5*(A(1)/V1-RMAX-KSS)+0.5*SQRT((A(1)/V1-RMAX-KSS)**2+4*KSS*A(1)/V=
*

1)

*>
*

*> DADT(1) =
*

*> -(K+K12)*CONC*V1+K21*A(2)-KINT*RMAX*CONC*V1/(KSS+CONC)-VM*CONC*V1/(KM+CON=
*

C)

*> DADT(2) = K12*CONC*V1-K21*A(2)
*

*>
*

*>
*

*> Thank you,
*

*>
*

*> Regards,
*

*> Niurys de Castro
*

*>
*

*> --
*

*>
*

*> MSc Niurys de Castro Suárez
*

*> Profesor Asistente Farmacometría
*

*> Investigador Agregado
*

*> Departamento Farmacia
*

*> Instituto de Farmacia y Alimentos, Universidad de La Habana
*

*> Cuba
*

*>
*

*>
*

Received on Sat Apr 06 2019 - 10:11:50 EDT

Date: Sat, 6 Apr 2019 10:11:50 -0400

Generally speaking, the portion which undergoes saturatable clearance due

to ligand or receptor engagement will be negligible at high concentrations.

Therefore, it is recommend to use one saturable equation without needs of

dose dependent “IF .. THEN … ENDIF “ Statement

The followings are some programming comments in NONMEM coding.

IF(DOS.LT.200) THEN;; This assumes DOSE below 50 and 100 not 200

;;; LT = less than

;;; LE = less than or Equal to

TVKM = THETA (5)

TVVM = THETA (6)

;; THIS needs to be end in order to next if Then statement effective

*ENDIF;;*

;;;

TVKSS = 0

TVKINT = 0

TVKDEG = 0

TVRMAX = 0

IF(DOS.GT.100) THEN;;; This assumes that DOS 200 and 400

;;; GT = Greater than

;;; GE = Great or Equal to

TVKSS = THETA (7)

TVKKINT = THETA(8)

TVRMAX = THETA(9)

ENDIF

....

$DES

CONC=0.5*(A(1)/V1-RMAX-KSS)+0.5*SQRT((A(1)/V1-RMAX-KSS)**2+4*KSS*A(1)/V1)

;; CONC is simply A(1)/V1 and RMAX and KSS are undefined variables.

Hope it helps.

On Tue, Apr 23, 2019 at 8:49 AM Niurys.CS <amaranthfan_at_gmail.com> wrote:

1)

C)

Received on Sat Apr 06 2019 - 10:11:50 EDT