The dosing design for the pig trial (S1), and the written code of the utilised model are described (S2), together with the fits of the median plasma concentration-time profiles of DON, 3ADON and 15ADON in broiler chickens and pigs (semi-log); circles=PO; diamonds=IV; blue=DON; green=3ADON; red=15ADON (S3).
Supplementary material S1. Schematic overview of the utilized cross-over design for the pig trial. By
subjecting each animal to 4 treatments a cross-over in six animals was obtained for each mycotoxin. This design allowed the use of half the animals needed for a traditional two-way cross-over experiment.
pigs 1st treatment 2nd treatment 3rd treatment 4th treatment
1-3 DON IV 15ADON IV DON PO 15ADON PO
4-6 3ADON PO DON IV 3ADON IV DON PO
7-9 15ADON IV 3ADON PO 15ADON PO 3ADON IV
Supplementary material S2. Model code for toxicokinetic analysis of DON, 3ADON and 15ADON after PO and IV
administration in broiler chickens, using WinNonlin Professional version 5.2.1.
Model 1
remark ****************************************************** remark Developer: Nathan Broekaert
remark Model Date: 18-04-2014 remark Model Version: 1.0
remark ****************************************************** remark
remark - define model-specific commands COMMANDS
NFUNCTIONS 4 NDERIVATIVES 7 NPARAMETERS 9
122 PNAMES 'Cldon', 'Cladon', 'Qdon', 'VCdon', 'VCadon', 'ka', 'FRAC', 'BioADON', 'VPdon'
END
remark - define temporary variables TEMPORARY TIME=X DOSPO=1689 DOSIV=1689 END
remark - define differential equations starting values START Z(1) = DOSIV/VCadon Z(2) = 0 Z(3) = 0 Z(4) = DOSPO*(1-FRAC) Z(5) = 0 Z(6) = 0 Z(7) = 0 END
remark - define differential equations DIFFERENTIAL
remark IV
DZ(1) = (-Cladon*Z(1))/VCadon
DZ(2) = (Cladon*Z(1) -Cldon*Z(2) -Qdon*Z(2) +Qdon*Z(3))/VCdon DZ(3) = (Qdon*Z(2) -Qdon*Z(3))/VPdon remark PO DZ(4) = -ka*BioADON*Z(4) -(ka*(1-BioADON)*Z(4)) DZ(5) = (BioADON*ka*Z(4) -CLadon*Z(5))/VCadon
DZ(6) = ((1-BioADON)*ka*Z(4) +CLadon*Z(5) -CLdon*Z(6) -Qdon*Z(6) +Qdon*Z(7))/VCdon DZ(7) = (Qdon*Z(6) -Qdon*Z(7))/VPdon
END
remark - define algebraic functions FUNCTION 1 F= Z(1) END FUNCTION 2 F= Z(2) END
123 FUNCTION 3 F= Z(5) END FUNCTION 4 F= Z(6) END
remark - define any secondary parameters remark - end of model
EOM
Supplementary material S3. Fits of the median plasma concentration-time profiles of DON, 3ADON and
15ADON in broiler chickens and pigs after IV and PO administration using a tailor-made toxicokinetic model in WinNonlin Professional version 5.2.1 (semi-log); circles=PO; diamonds=IV; blue=DON; green=3ADON; red=15ADON.
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