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NONMEM 7 Pharmacokinetic (PREDPP) Models and Parameters

ADVAN Compartments TRANS Basic Parameters Additional Parameters


ADVAN1 1 = Central TRANS1 K S1, S2, F1, F0, ALAG1
2 = Output TRANS2 CL, V
1 = Depot TRANS1 KA, K
ADVAN2 2 = Central S1, S2, S3, F1, F2, F0, ALAG1
TRANS2 CL, V, KA
3 = Output
TRANS1 K, K12, K21
1 = Central
TRANS3 CL, V, Q, VSS S1, S2, S3, F1, F2, F0, ALAG1,
ADVAN3 2 = Peripheral
TRANS4 CL, V1, Q, V2 ALAG2
3 = Output
TRANS5 AOB, ALPHA, BETA
1 = Depot TRANS1 KA, K, K23, K32
2 = Central TRANS3 CL, V, Q, VSS, KA S1, S2, S3, S4, F1, F2, F3, F0,
ADVAN4
3 = Peripheral TRANS4 CL, V2, Q, V3, KA ALAG1, ALAG2, ALAG3
4 = Output TRANS5 AOB, ALPHA, BETA, KA
General linear models
(user-defined) User-defined (eg K10, K12, Sn, Fn, ALAGn
ADVAN5 (TRANS1)
eg COMP = (CENTRAL), K21, K10=CL/V) (dependent on model definition)
COMP = (PERIPH)
General nonlinear
models (user-defined) User-defined (eg KA, VC, Sn, Fn, ALAGn
ADVAN6 (TRANS1)
eg COMP = (CENTRAL), EMAX) (dependent on model definition)
COMP = (PERIPH)
General linear models
ADVAN7 with real Eigenvalues, (TRANS1) Same ad ADVAN5 Same as ADVAN5
similar to ADVAN5
General nonlinear
models with stiff
ADVAN8 (TRANS1) Same ad ADVAN6 Same as ADVAN6
equations, similar to
ADVAN6
General nonlinear
models with equilibrium
ADVAN9 (TRANS1) Same ad ADVAN6 Same as ADVAN6
compartments, similar
to ADVAN6
1 = Central
ADVAN10 (TRANS1) VM, KM S1, S2, F1, F0, ALAG1
2 = Output
1 = Central TRANS1 K, K12, K21, K13, K31
2 = Peripheral1 TRANS4 CL, V1, Q2, V2, Q3, V3 S1, S2, S3, S4, F1, F2, F3, F0,
ADVAN11
3 = Peripheral2 ALPHA, BETA, GAMMA, ALAG1, ALAG2, ALAG3
4 = Output TRANS6
K21, K31
1 = Depot TRANS1 K, K23, K32, K24, K42, KA
2 = Central TRANS4 CL, V2, Q3, V3, Q4, V4, KA S1, S2, S3, S4, F1, F2, F3, F0,
ADVAN12 3 = Peripheral1
ALPHA, BETA, GAMMA, ALAG1, ALAG2, ALAG3
4 = Peripheral2 TRANS6
K32, K42, KA
5 = Output
General nonlinear
models with stiff
ADVAN13 (TRANS1) Same ad ADVAN6 Same as ADVAN6
equations, similar to
ADVAN6

© 2011 PK/PD Associates


NMTRAN Control Stream Records
$COVARIANCE Command to calculate the standard error of the parameter estimates and a
correlation matrix. Options include MATRIX=S or R.
$DATA Name of the data file to be used. Specific rows can be ignored using
IGNORE=C or IGNORE=(ID.EQ.12). Specific number of rows to be read in
can be done with RECORDS=n.
$DES Specifies differential equations to be used in the model. DADT(n) is the
change in the Amount in compartment n with time ( dA dt ). A differential
equation must be specified for all compartments.
$ERROR Specifies the random residual, within-individual error model structure and
associated EPSILONS (EPS or ERR). Allows coding of concentration-effect
relationships in PK/PD models. €
$ESTIMATION Sets conditions for the estimation of parameters. Options include PRINT=n
(number of iterations between screen output), NOABORT, MAXEVAL=n,
METHOD=x, POSTHOC, and others.
$INPUT List of items or columns in the dataset. Labels do NOT have to match labels
in the dataset, but the order of appearance is critical. Reserved labels: ID,
DV, MDV, TIME, EVID, AMT RATE, SS II, ADDL, CMT, PCMT, CALL,
CONT, DATE, DAT1, DAT3, L1, L2.
$MODEL Required for ADVAN5-ADVAN9 and ADVAN13. Specifies model structure
for user-defined models. NPARAMETERS=n and COMP=(attributes) are
required. Attributes include DEFDOSE (default dose), DEFOBS (default
observation, OBS (observation), INITIALOFF (start amount at 0), and others.
$OMEGA Specifies initial estimates of the variance of the first level of random error.
For individual models this represents residual (within-individual) error. For
population models this represents between-individual errors (ETAs).
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Variance of ETA is called OMEGA .
$PK Assigns the THETAs to fixed effect parameters. Specifies random between-
individual effect models (ETAs). Reparameterizes structural model
parameters (eg CL=K10/V).
$PRED Used only when a specific ADVAN is not used. Y is required and is the
modeled value for the dependent variable (eg Y = m * x + b ).
$PROBLEM Problem description or title for identfication purposes. Not used by
NONMEM, but incorporated into PDx-Pop’s model output information.
$SIGMA Specifies initial estimates of the variance of the second level of random error.
Not used in individual models. For population
€ models this represents the
residual (within-individual) error (EPSILONs). Variance of EPSILON is called
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SIGMA .
$SIMULATION Command to execute a simulation. Must include random seed integer
between 0 and 2147483647. Use ONLYSIMULATION to avoid evaluating
objective function at each step. Use SUBPROBLEMS=n to repeat the
simulation n times.
$SUBROUTINE Specifies which PREDPP model is to be used (ADVANn TRANSn)
$THETA Specifies initial estimates and bounds of fixed effects parameters:
(lower, initial, upper)
$TABLE Specifies table output to be generated. The following variables are output by
default: DV (dependent variable), PRED (prediction of DV), RES (residual
[PRED-DV]), WRES (weighted residual [RES/PRED]). User can specify any
other variable for output. Options include ONEHEADER, NOPRINT, and
FILE=filename. Output is a space-delimited text file.

© 2011 PK/PD Associates