Init is the initial estimate. If FIXED is used, the final parameter estimate is to be constrained to equal the initial parameter estimate.

Low and up are lower and upper bounds respectively. They are the boundaries for the minimization search. Commas are optional. If an upper bound is used, a lower bound must also be used (e.g., -INF; see below). The lower and upper bounds (or if just the lower bound is used, then just this bound) may be omitted, in which case this form differs from the one described above only in so far as with this form, the initial estimate and the FIXED attribute are enclosed in parentheses. When FIXED is used, and a bound appears the bound must equal the initial estimate. FIXED is implied when all three values are equal. The lower bound can be -INF (negative infinity), and the upper bound can be INF (infinity). They are the defaults for lower and upper bounds. ¹

This is just like the form described above except that if the FIXED attribute is used, the attribute occurs outside the parentheses, and then if moreover, a bound appears, the bound need not equal the initial estimate.

The commas are required. Because no initial estimate is given, a search for an initial estimate (the Initial Estimates Step) is undertaken by NONMEM. With NONMEM 7.4, when initial THETAs are to be estimated, evaluations can now be done for FOCE and Laplace, not just for FO.

Any initial value or group of initial values may be enclosed in parentheses and followed by "xn", which means to replicate the values within parentheses n times ("repeated value"). The values within the parenthesis may have any of the above forms. For example, the following two are equivalent:

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$THETA 2 2 2 2 (0.001,0.1,1000) (0.001,0.1,1000) (0.001,0.1,1000) (0.5 FIXED) (0.5 FIXED)
$THETA (2)x4 (0.001,0.1,1000)x3 (0.5 FIXED)x2

UNINT is used during the Optimal Design Step to identify a theta as uninteresting. UNINT may be used anywhere that FIXED may be used.

This is a compact method of defining an element of theta, specifying its initial estimate, and specifying a symbolic index for this element of THETA. The symbolic index may be used for THETA in abbreviated code, and will also identify this element of THETA in the NONMEM output. (Only the first 9 characters of the label will appear). If new $THETA records change the ordering, the abbreviated code does not have to be changed. For example, suppose the third element of THETA that is defined happens to be

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3

$THETA
CL=(0.0,7.0)
V1=(5.0 fixed)

Once defined, the $PK or $PRED code can use these definitions:

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TVCL=THETA(CL)

The NONMEM report will describe the relationship,

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2

    LABELS FOR THETAS THETA(3)=THETA(CL)
    and THETA(CL) rather than TH 3 will appear in the NONMEM report.

Alternatively one can specify the label using

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  $ABBR REPLACE THETA(CL)=THETA(1)
  $ABBR REPLACE THETA(V1)=THETA(2)

control record but the NONMEM report will not identify the relationship and will not generate the symbolic label THETA(CL) in the report. For dynamic, or implicit mapping of labels, such as for various occasions, these still need to be done via the $ABBR REPLACE record.

$THETA records must be placed ahead of any records that use the symbolic label. Therefore these records must be placed before $THETAI, $THETAR, and abbreviated code.

A compact way of defining one or more THETAs with labels and initial values. For example

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$THETA NAMES(V1,CL,Q,V2) (0.0,7.0) (0.0,7.0) (0.0,7.0) 7

During NONMEM's search for an initial estimate, a number of points will be examined. This number will be automatically determined by NONMEM, or it can be specified with this option. May also be coded NUMBERPTS, NUMPOINTS, NUMPTS.

ABORT: during the Initial Estimates step, NONMEM is to abort when PRED sets the error return code to 1. (The PRED error return code n is set by the statement "EXIT n [k]" in abbreviated code, or by the statement IERPRD=n in user-supplied code, or by PREDPP when it detects an error.) This is the default.

NOABORT: during the Initial Estimates step, NONMEM is simply to ignore values of the theta vector that result in PRED error return code 1. (Ordinarily the first value of the theta vector is never ignored.) These will not be feasible values for an initial estimate.

NOABORTFIRST: Same as NOABORT option, but also applies to the first value of the theta vector that is tried. It cannot be shortened; all characters must be coded. May be used with the NOABORT option, in which case the stronger condition (NOABORTFIRST) takes precedence.