{UTF-8}
********************************************************
	.Thalidomid
********************************************************~
		Simulation: Peter Bützer
	|

Dosis=
	100
	~	mg [50,400,50]
	~		|

R2= INTEG (
	+Rr+RSi-Re+SRi,
		0)
	~	mg [0,?]
	~	Menge R-Isomer  im Blut
	|

S2= INTEG (
	+Sr-RSi-Se-SRi,
		0)
	~	mg [0,?]
	~	Menge S-Isomer  im Blut
	|

kisr=
	LN(2)/HWZsr
	~	1/Hour
	~		|

HWZsr=
	3.75
	~	Hour [0,6]
	~	k=ln(0.25)/7.5=0.1848, HWZ=ln(2)/0.1848=3.75
	|

R1= INTEG (
	-Rr,
		Dosis*(1-"RS-S")*0.4)
	~	mg [0,?]
	~	Menge R-Isomer  im Verdauungstrakt; Biologische Verfügbarkeit: 40% --> 0.4
	|

S1= INTEG (
	-Sr,
		Dosis*"RS-S"*0.4)
	~	mg [0,?]
	~	Menge S-Isomer im Verdauungstrakt; Biologische Verfügbarkeit: 40% --> 0.4
	|

SRi=
	kisr*S2
	~	mg/Hour
	~		|

krr=
	LN(2)/HWZr
	~	1/Hour [0,?]
	~	Reaktionsgeschwindigkeits-Konstante der Resorption
	|

kse=
	LN(2)/HWZe
	~	1/Hour [0,?]
	~	Reaktionsgeschwindigkeits-Konstante der Elimination des S-Isomers
	|

HWZr=
	0.75
	~	Hour [0.5,2]
	~	Der maximale Plasmaspiegel wird in 2.9 - 5.7 Stunden erreicht (Mittelwert: \
		4h); daraus ergibt sich für das Racemat k=0.75
	|

ksr=
	LN(2)/HWZr
	~	1/Hour [0,?]
	~	Reaktionsgeschwindigkeits-Konstante der Resorption
	|

HWZe=
	12
	~	Hour [8,15]
	~		|

kre=
	LN(2)/HWZe
	~	1/Hour [0,?]
	~	Reaktionsgeschwindigkeits-Konstante der Elimination des R-Isomers
	|

HWZrs=
	2.5
	~	Hour [0,5]
	~	k=ln(0.25)/5=0.2773, HWZ=ln(2)/0.2773=2.5
	|

krs=
	LN(2)/HWZrs
	~	1/Hour [0,?]
	~	Reaktionsgeschwindigkeits-Konstante der Inversion R-> S
	|

"RS-S"=
	1
	~	Dmnl [0.5,1]
	~	Reines S-Isomer=1, reines Racemat 0.5
	|

RSi=
	-krs*R2
	~	mg/Hour
	~		|

Re=
	kre*R2
	~	mg/Hour
	~		|

Rr=
	krr*R1*0.4
	~	mg/Hour
	~	0.4: Biolog. Verfügbarkeit
	|

Se=
	kse*S2
	~	mg/Hour
	~		|

Sr=
	ksr*S1
	~	mg/Hour
	~	0.4: Biolog. Verfügbarkeit
	|

********************************************************
	.Control
********************************************************~
		Simulation Control Parameters
	|

FINAL TIME  = 72
	~	Hour
	~	The final time for the simulation.
	|

INITIAL TIME  = 0
	~	Hour
	~	The initial time for the simulation.
	|

SAVEPER  = 
        TIME STEP 
	~	Hour [0,?]
	~	The frequency with which output is stored.
	|

TIME STEP  = 0.1
	~	Hour [0,?]
	~	The time step for the simulation.
	|

\\\---/// Sketch information - do not modify anything except names
V300  Do not put anything below this section - it will be ignored
*View 1
$192-192-192,0,Times New Roman|12||0-0-0|0-0-0|0-0-255|-1--1--1|-1--1--1|120,120,100,0
10,1,R1,236,136,40,20,3,3,0,0,0,0,0,0
10,2,S1,238,261,40,20,3,3,0,0,0,0,0,0
10,3,R2,432,136,40,20,3,3,0,0,0,0,0,0
10,4,S2,438,258,40,20,3,3,0,0,0,0,0,0
1,5,7,3,36,0,0,22,2,0,0,-1--1--1,|12||0-0-0,1|(406,173)|
1,6,7,4,68,0,0,22,2,0,0,-1--1--1,|12||0-0-0,1|(406,220)|
11,7,252,406,196,8,6,33,3,0,0,4,0,0,0
10,8,RSi,434,196,20,11,40,131,0,0,-1,0,0,0
1,9,11,3,4,0,0,22,0,0,0,-1--1--1,,1|(366,136)|
1,10,11,1,100,0,0,22,0,0,0,-1--1--1,,1|(302,136)|
11,11,204,334,136,6,8,34,3,0,0,1,0,0,0
10,12,Rr,334,156,19,12,40,3,0,0,-1,0,0,0
1,13,15,4,4,0,0,22,0,0,0,-1--1--1,,1|(369,261)|
1,14,15,2,100,0,0,22,0,0,0,-1--1--1,,1|(303,261)|
11,15,188,335,261,6,8,34,3,0,0,1,0,0,0
10,16,Sr,335,281,17,12,40,3,0,0,-1,0,0,0
12,17,48,632,136,10,8,0,3,0,0,-1,0,0,0
1,18,20,17,4,0,0,22,0,0,0,-1--1--1,,1|(582,136)|
1,19,20,3,100,0,0,22,0,0,0,-1--1--1,,1|(501,136)|
11,20,48,536,136,6,8,34,3,0,0,1,0,0,0
10,21,Re,536,156,13,12,40,3,0,0,-1,0,0,0
12,22,48,634,262,10,8,0,3,0,0,-1,0,0,0
1,23,25,22,4,0,0,22,0,0,0,-1--1--1,,1|(582,263)|
1,24,25,4,100,0,0,22,0,0,0,-1--1--1,,1|(503,263)|
11,25,48,535,263,6,8,34,3,0,0,1,0,0,0
10,26,Se,535,283,12,12,40,3,0,0,-1,0,0,0
1,27,3,20,1,0,0,0,0,64,0,-1--1--1,,1|(496,92)|
1,28,4,25,1,0,0,0,0,64,0,-1--1--1,,1|(499,230)|
1,29,3,7,1,0,0,0,0,64,0,-1--1--1,,1|(368,152)|
1,30,1,11,1,0,0,0,0,64,0,-1--1--1,,1|(300,92)|
1,31,2,15,1,0,0,0,0,64,0,-1--1--1,,1|(298,231)|
10,32,krs,336,195,20,10,8,131,0,0,0,0,0,0
10,33,krr,270,59,17,12,8,3,0,0,0,0,0,0
10,34,ksr,260,318,33,13,8,131,0,0,0,0,0,0
10,35,kse,459,326,16,12,8,3,0,0,0,0,0,0
10,36,kre,488,56,15,12,8,3,0,0,0,0,0,0
1,37,36,20,1,0,0,0,0,64,0,-1--1--1,,1|(536,87)|
1,38,35,26,1,0,0,0,0,64,0,-1--1--1,,1|(505,325)|
1,39,34,16,1,0,0,0,0,64,0,-1--1--1,,1|(317,321)|
1,40,33,11,1,0,0,0,0,64,0,-1--1--1,,1|(331,90)|
1,41,32,7,1,0,0,0,0,64,0,-1--1--1,,1|(363,176)|
10,42,HWZrs,246,198,44,17,8,131,0,0,0,0,0,0
1,43,42,32,1,0,0,0,0,64,0,-1--1--1,,1|(290,175)|
10,44,"RS-S",95,257,23,12,8,3,0,0,0,0,0,0
10,45,HWZe,411,78,32,12,8,3,0,0,0,0,0,0
1,46,45,36,1,0,0,0,0,64,0,-1--1--1,,1|(445,57)|
1,47,45,35,1,0,0,0,0,64,0,-1--1--1,,1|(404,278)|
10,48,HWZr,145,186,27,12,8,3,0,0,0,0,0,0
1,49,48,33,1,0,0,0,0,64,0,-1--1--1,,1|(169,110)|
1,50,48,34,1,0,0,0,0,64,0,-1--1--1,,1|(188,288)|
10,51,HWZsr,610,206,31,12,8,3,0,0,0,0,0,0
10,52,kisr,547,211,17,12,8,3,0,0,0,0,0,0
1,53,51,52,1,0,0,0,0,64,0,-1--1--1,,1|(585,180)|
1,54,56,3,4,0,0,22,0,0,0,-1--1--1,,1|(462,175)|
1,55,56,4,100,0,0,22,0,0,0,-1--1--1,,1|(462,222)|
11,56,300,462,200,8,6,33,3,0,0,4,0,0,0
10,57,SRi,487,200,17,12,40,3,0,0,-1,0,0,0
1,58,52,56,1,0,0,0,0,64,0,-1--1--1,,1|(511,181)|
1,59,4,56,1,0,0,0,0,64,0,-1--1--1,,1|(498,220)|
10,60,Dosis,112,98,25,12,8,3,0,0,0,0,0,0
12,61,0,920,632,332,204,3,188,0,0,1,0,0,0
Vergleich
1,62,44,1,0,0,0,0,0,64,1,-1--1--1,,1|(154,205)|
1,63,60,1,0,0,0,0,0,64,1,-1--1--1,,1|(159,111)|
1,64,44,2,0,0,0,0,0,64,1,-1--1--1,,1|(151,257)|
1,65,60,2,0,0,0,0,0,64,1,-1--1--1,,1|(167,169)|
///---\\\
:GRAPH GRAPH
:TITLE Vergleich
:X-AXIS Time
:SCALE
:VAR S2|S-Form
:Y-MIN 0
:Y-MAX 0.5
:DATASET S-Form
:SCALE
:VAR R2|Racemat
:Y-MIN 0
:Y-MAX 0.5
:DATASET Racemat

:GRAPH Vergleich
:TITLE Vergleich
:X-AXIS Time
:X-LABEL Stunden
:SCALE
:VAR R2|R-Enantiomer
:UNITS mg
:VAR S2|S-Enatniomer
:UNITS mg
:L<%^E!@
9:Current
23:0
15:0,0,0,0,0,0
19:100,0
27:2,
34:0,
5:Dosis
24:0
25:0
26:0