Objectives
- To observe the time course of drug concentration in the centrl and peripheral compartments
of a two-compartment system.
- To compare the time course after 3 types of input.
a. Single Bolus Dose
b. Single Bolus Dose and
Constant Rate Infusion
c. Single Bolus Dose plus First-Order and Constant Rate Infusion
Introduction
This is a practical session held in a laboratory. For health and safety reasons
it is important to wear a lab coat and closed shoes.
Bring a printed copy of the lab instructions and read through them before you arrive
at the lab. You will also find it useful to look at the MLX-TRAN code for the 2 compartment model.
Overview
- Start the experiment by adding doses of amaranth dye to the beaker system.
- Take samples from the central and tissue compartment beakers.
- Measure the absorbance of the samples using a spectrophotometer.
- Plot the time course of absorbance while the experiment is being performed,
- Construct a standard curve relating absorbance to amaranth dye concentrations on
two occasions.
- Use MONOLIX and the beka_mlxt model (Figure 1) to estimate the parameters of the two compartment system.
$PROBLEM BEKA two compartment model with
bolus, zero-order and first-order input
$MODEL
COMP=(AMTC) ; central
COMP=(AMTT) ; tissue
COMP=(AMTB) ; burette
$PSI
cl vc clic vt ; PK parameters
$PK
bolus=10 ; 10 mg bolus dose into central compartment
infrate=1 ; 1 mg/min infusion into burette
burdose=40 ; 40 mg bolus dose into burette
burvol=0.1 ; 0.1 L burette volume
burflow=0.01 ; 0.01 L/min burette flow
tk0=30 ; 30 min infusion from burette
$ODE
AMTC_0 = bolus
AMTT_0 = 0
AMTB_0 = infrate/burflow*burvol+burdose
CC=AMTC/vc
CT=AMTT/vt
CB=AMTB/burvol
;'t' is the name used by Monolix
;to refer to the data item defined as TIME.
if (t<tk0) then
ratein=burflow*CB
else
ratein=0
endif
DDT_AMTC = ratein + clic*CT - (cl+clic)*CC
DDT_AMTT = clic*(CC - CT)
DDT_AMTB = infrate - ratein
$OUTPUT
OUTPUT1 = AMTC/vc
OUTPUT2 = AMTT/vt
Figure 1. Code for beka_mlxt.txt
