**From: "Piotrovskij, Vladimir" <vpiotrov@janbe.jnj.com>
**

Dear Alison,

I fitted ADVAN2 TRANS1 model to my data using two parameterizations: with V and CL which should give identical results. However, it was not so. The first one:

$PK

K = THETA(1) * EXP(ETA(1))

V = THETA(2) * EXP(ETA(2))

KA = THETA(3) * EXP(ETA(3))

TLAG = 0

IF (TRT.NE.1) TLAG=THETA(4)

ALAG1= TLAG * EXP(ETA(4))

S2 = V

CL = K*V

$EST MAX=9000 NOABORT METHOD=1 INTERACTION

It converged at 733.243 with the following estimates of THETA

TH 1 TH 2 TH 3 TH 4

9.27E-02 2.16E+02 4.57E+00 2.01E-01

The alternative parameterization:

$PK

K = THETA(1) * EXP(ETA(1))

CL = THETA(2) * EXP(ETA(2))

KA = THETA(3) * EXP(ETA(3))

TLAG = 0

IF (TRT.NE.1) TLAG=THETA(4)

ALAG1= TLAG * EXP(ETA(4))

V = CL/K

S2 = V

$EST MAX=9000 NOABORT METHOD=1 INTERACTION

It converged at 747.266, and estimates were

TH 1 TH 2 TH 3 TH 4

9.27E-02 2.00E+01 4.60E+00 2.06E-01

The rest of the NM-TRAN code was the same. What's also strange: the elapsed CPU time for the first version was about 6 min while for the second version more than 6 h.

Am I missing something?

TIA,

Vladimir

----------------------------------------------------------------------

Vladimir Piotrovsky, Ph.D.

Janssen Research Foundation

Clinical Pharmacokinetics

B-2340 Beerse

Belgium

Fax: +32-14-605834

Email: vpiotrov@janbe.jnj.com

vpiotrov@janbelc1.ssw.jnj.com