Comparative study of NONMEM and WinNonMix in the population pharmacokinetics of benznidazol
Peregrina-Lucano A.A.1,2, Martín-Suárez A.1, García L.R.2, González M.H.2, Garcia M.J.1, Lanao J.M.1
1) Department of Pharmacy and Pharmaceutical Technology. University of Salamanca, Spain. 2) Department of Pharmacobiology. Laboratory of Investigation and Development Pharmaceutical. University of Guad alajara, Mexico.
The objective of the present study was compare the population pharmacokinetics parameters of tripanomicide Benznidazol using the NONMEM a nd WinNonMix programs.
The study was carried out in a population of 11 volunteers (5 male, 6 female, age:23.27± 9.24 years, weigth:63.54± 7.84Kg). A single oral dose of Benznidazol in two successive treatments was administered in absence and food presence with a wash period of 7 days. The blood samples was drawn to following times: 0.25, 0.50, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6. 0, 8.0, 12.0, 24.0, 36.0 and 48.0 hours. The analytical technique used was HPLC with a reverse phase and a UV detection.
The structural pharmacokinetic model utilized was one com partment with first order absorption and elimination. The error model selectioned was Proportional, to interindividual variability and residual variability. The covariates enclosed in the population model; sex (0=male, 1=female) and food influence (0=fasting, 1=food), were selectioned by backward/forward technique for a probability level of 99% (p<0.01). The final model obtained with both programs was:
Ka=
q 1 Ke=q 2*(1+q 3*SEX) Vd=q 4*(1+q 5*DIET)|
Ka (hr-1) |
Ke (hr-1) |
Vd (l) |
||||||||
|
q 1 |
h |
q 2 |
q 3 |
h |
q 4 |
q 5 |
h |
e |
Objective F. | |
|
NONMEM |
1.10 |
181% |
0.036 |
0.27 |
19% |
46.1 |
0.10 |
30% |
24% |
-235.344 |
|
Std Error |
14.1% |
29.8% |
12.2% |
52.6% |
53.8% |
96.3% |
142.6% |
20.3% |
23.3% |
|
|
WinNonMix |
1.10 |
181% |
0.036 |
0.27 |
19% |
46.1 |
0.10 |
30% |
24% |
-235.269 |
|
Std Error |
40.2% |
7.78% |
48.3% |
9.75% |
148.9% |
The parameters of fixed and random effects do not show si gnificative difference between kind of software, but show difference in standard error.