The $AES record is used to compute algebraic expressions which can be regarded as specifying equilibrium kinetics. It is used with PREDPP's ADVAN9, ADVAN15 and ADVAN17.

(See $AESINIT).

The complete AES routine can be divided into two parts: code which computes the amounts in the equilibrium compartments at the beginning of the integration interval (these amounts depend on the amounts in the nonequilibrium compartments) and code which computes values for the right sides of the algebraic equations. An abbreviated code for AES is actually divided into two abbreviated codes which correspond to the two parts of the complete AES routine. This record gives an abbreviated code for the second part of the AES routine. The $AESINITIAL record gives an abbreviated code for the first part. The $AES record, along with all its continuation records, is called a $AES block.

This record is optional. If it appears, it must be with the first problem specification, and only this problem specfication. If there are no equilibrium compartments, but ADVAN9 or ADVAN15 is used, the record need not appear. It may not appear when the MODEL routine is user-supplied. Implicit basic PK param- eters may be used in the $AES block (see below) only when the $PK block precedes the $AES block.

The mandatory left-hand quantities are values of expressions which when set to 0, constitute the system of algebraic equations describing the equilibrium kinetics. They are symbolized by E(n). The number n must be an equilibrium compartment number. However, there need not be any particular relationship between the indices and the equilibrium compartments. At least one such quantity must be computed.

Symbolic differentiation is used to obtain code used in the generated subroutine to compute the elements of the DA, DP, and DT arrays.

See abbreviated code for general rules. Specific rules follow.

• E(ncm1+i), E(ncm1+2), … (Required. Expressions which, when set to 0, constitute the system of algebraic expressions describing the equilibrium kinetics. ncm1 is the number of nonequilibrium compartments.) The indices "(…)" may be omitted, in which case NM-TRAN will supply them according to the order in which the expressions appear. Indices are required when the expressions are defined conditionally (i.e., using an IF statement).
• AES-defined (i.e., PRED-defined) items.

• A(1), A(2), … (Current compartment amounts; may be random variables.)
• P(1), P(2), … (Post-translation basic PK parameters; may be random variables.)
• PK-defined items (Implicit basic PK parameters; may be random variables.)
• T (Time; may be random variable. T takes values continuously over an integration interval.)
• AES-defined variables that appeared earlier as left-hand quantities in $AES, and similarly from the $AESINITIAL record. (Caution: AESINITIAL-defined variables that depend on compartment amounts will depend on the initial values of these compartment amounts, not the current values.)
• Data item labels specified on the $INPUT statement.
• THETA(n).
• Global Variables in Modules: certain variables in FORTRAN modules can be used.

The following are of particular interest.

• DOSTIM: DOSTIM is the time of a lagged dose or additional dose to which the system is being advanced. Abbreviated code in $AES may test DOSTIM. It may use DOSTIM on the right, unless DOSTIM is a random variable. However, it may be used on the right in a $PK block to define a random variable which may in turn be used on the right in the $AES block.
• DOSREC: DOSREC is the dose record corresponding to the dose entering at DOSTIM. Abbreviated code in $AES may test items in DOSREC in a logical condition, and DOSREC may always be used on the right.
• ISFINL: During simulation or a copying pass, and during the advance to a particular time (event or non-event time), ISFINL=1 at a final call to AES at that time. Otherwise, ISFINL=0.

Forbidden Variable Names: IR DA DP DT ETA(n) EPS(n) ERR(n)

• Follows $SUBROUTINES $INPUT $MODEL $PK
• Follows $AESINITIAL

(See AES)