NONLINEAR MIXED EFFECTS MODEL PROGRAM (NONMEM), VERSION V LEVEL 1.0 DEVELOPED AND PROGRAMMED BY STUART BEAL AND LEWIS SHEINER ************************* RUN SUMMARY ************************* PROBLEM NUMBER 01, Karmakar Data DATA CHECKOUT RUN: NO NUMBER OF DATA RECORDS IN DATA SET: 814 NUMBER OF DATA ITEMS IN DATA SET: 11 ID DATA ITEM IS DATA ITEM NO.: 1 DEP VARIABLE IS DATA ITEM NO.: 9 MDV DATA ITEM IS DATA ITEM NO.: 10 INDICES PASSED TO SUBROUTINE PRED: 11 7 0 0 0 0 0 0 0 0 0 LABELS FOR DATA ITEMS: ID AGE WT HT GRP AV TIME C LGC MDV EVID (NONBLANK) LABELS FOR PRED-DEFINED ITEMS: BIO1 MAT1 CV1 BIO2 MAT2 CV2 KAV DOSE LTY FORMAT FOR DATA: (10E7.0,1F2.0) TOTAL NUMBER OF OBSERVATION RECORDS: 794 TOTAL NUMBER OF INDIVIDUALS: 20 LENGTH OF THETA: 8 OMEGA HAS SIMPLE DIAGONAL FORM WITH DIMENSION: 7 SIGMA HAS SIMPLE DIAGONAL FORM WITH DIMENSION: 1 INITIAL ESTIMATE OF THETA: LOWER BOUND INITIAL EST UPPER BOUND 0.5500E+00 0.5500E+00 0.5500E+00 0.7100E+00 0.7100E+00 0.7100E+00 0.1830E+02 0.1830E+02 0.1830E+02 0.5530E+01 0.5530E+01 0.5530E+01 0.8250E+00 0.8250E+00 0.8250E+00 0.7150E+03 0.7150E+03 0.7150E+03 0.1140E+01 0.1140E+01 0.1140E+01 0.4460E+00 0.4460E+00 0.4460E+00 INITIAL ESTIMATE OF OMEGA: 0.1000E+00 0.0000E+00 0.1000E+00 0.0000E+00 0.0000E+00 0.1000E+00 0.0000E+00 0.0000E+00 0.0000E+00 0.1000E+00 0.0000E+00 0.0000E+00 0.0000E+00 0.0000E+00 0.1000E+00 0.0000E+00 0.0000E+00 0.0000E+00 0.0000E+00 0.0000E+00 0.1000E+00 0.0000E+00 0.0000E+00 0.0000E+00 0.0000E+00 0.0000E+00 0.0000E+00 0.1000E+00 INITIAL ESTIMATE OF SIGMA: 0.3900E-01 ESTIMATION STEP OMITTED: NO POP. ETAS OBTAINED POST HOC: YES NUMBER OF FUNCTION EVALUATIONS ALLOWED: 2000 NUMBER OF SIGNIFICANT FIGURES REQUIRED: 3 INTERMEDIATE PRINTOUT: YES ESTIMATE OUTPUT TO MSF: NO ABORT WITH PRED EXIT CODE 1: NO TABLES STEP OMITTED: NO NUMBER OF TABLES: 1 -- TABLE 1 -- PRINTED: YES USER-CHOSEN ITEMS IN THE ORDER THEY WILL APPEAR IN THE TABLE: ID DOSE GRP AV KAV BIO1 MAT1 CV1 BIO2 MAT2 CV2 TIME LTY DOUBLE PRECISION PREDPP VERSION IV LEVEL 1.0 GENERAL NONLINEAR KINETICS MODEL (ADVAN6) MODEL SUBROUTINE USER-SUPPLIED - ID NO. 9999 MAXIMUM NO. OF BASIC PK PARAMETERS: 11 COMPARTMENT ATTRIBUTES COMPT. NO. FUNCTION INITIAL ON/OFF DOSE DEFAULT DEFAULT STATUS ALLOWED ALLOWED FOR DOSE FOR OBS. 1 CENTRAL ON YES YES YES YES 2 PERIPH ON YES YES NO NO 3 VENOUS ON YES YES NO NO 4 OUTPUT OFF YES NO NO NO NRD VALUE FROM SUBROUTINE TOL: 3 1 ADDITIONAL PK PARAMETERS - ASSIGNMENT OF ROWS IN GG COMPT. NO. INDICES SCALE BIOAVAIL. ZERO-ORDER ZERO-ORDER ABSORB FRACTION RATE DURATION LAG 1 * * * * * 2 * * * * * 3 * * * * * 4 * - - - - - PARAMETER IS NOT ALLOWED FOR THIS MODEL * PARAMETER IS NOT SUPPLIED BY PK SUBROUTINE; WILL DEFAULT TO ONE IF APPLICABLE DATA ITEM INDICES USED BY PRED ARE: EVENT ID DATA ITEM IS DATA ITEM NO.: 11 TIME DATA ITEM IS DATA ITEM NO.: 7 PK SUBROUTINE CALLED ONCE PER INDIVIDUAL RECORD. PK SUBROUTINE NOT CALLED AT NONEVENT (ADDITIONAL OR LAGGED) DOSE TIMES. ERROR SUBROUTINE CALLED WITH EVERY EVENT RECORD. DES SUBROUTINE USES COMPACT STORAGE MODE MONITORING OF SEARCH: ITERATION NO.: 0 OBJECTIVE VALUE: -1153.7714 ITERATION NO.: 1 OBJECTIVE VALUE: -1204.6381 ITERATION NO.: 2 OBJECTIVE VALUE: -1229.0744 ITERATION NO.: 3 OBJECTIVE VALUE: -1229.6098 ITERATION NO.: 4 OBJECTIVE VALUE: -1234.3823 ITERATION NO.: 5 OBJECTIVE VALUE: -1234.8254 ITERATION NO.: 6 OBJECTIVE VALUE: -1235.3092 ITERATION NO.: 7 OBJECTIVE VALUE: -1237.6948 ITERATION NO.: 8 OBJECTIVE VALUE: -1238.3619 ITERATION NO.: 9 OBJECTIVE VALUE: -1255.3941 ITERATION NO.: 10 OBJECTIVE VALUE: -1257.9313 ITERATION NO.: 11 OBJECTIVE VALUE: -1258.9183 ITERATION NO.: 12 OBJECTIVE VALUE: -1259.0983 ITERATION NO.: 13 OBJECTIVE VALUE: -1259.1677 ITERATION NO.: 14 OBJECTIVE VALUE: -1259.2124 ITERATION NO.: 15 OBJECTIVE VALUE: -1259.2569 ITERATION NO.: 16 OBJECTIVE VALUE: -1259.2871 ITERATION NO.: 17 OBJECTIVE VALUE: -1259.2987 ITERATION NO.: 18 OBJECTIVE VALUE: -1259.3005 ITERATION NO.: 19 OBJECTIVE VALUE: -1259.3007 ITERATION NO.: 20 OBJECTIVE VALUE: -1259.3007 ITERATION NO.: 21 OBJECTIVE VALUE: -1259.3007 ITERATION NO.: 22 OBJECTIVE VALUE: -1259.3011 ITERATION NO.: 23 OBJECTIVE VALUE: -1259.3011 ITERATION NO.: 24 OBJECTIVE VALUE: -1259.3011 MINIMIZATION SUCCESSFUL NO. OF FUNCTION EVALUATIONS USED: 104 NO. OF SIG. DIGITS IN FINAL EST.: 4.0