Professor Nick Holford
Department of Pharmacology & Clinical Pharmacology, FMHS, University of Auckland Professor Nick Holford
Department of Pharmacology & Clinical Pharmacology, FMHS, University of Auckland

Two compartment beaker model

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Objective and introduction

Objectives

  1. To observe the time course of drug concentration in the centrl and peripheral compartments of a two-compartment system.
  2. To compare the time course after 3 types of input.
    1. Single Bolus Dose
    2. Single Bolus Dose and Constant Rate Infusion
    3. 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.

Lab coat and shoes required 

Bring a printed copy of the lab instructions and read through them before you arrive at the lab.

Overview and assignment

Overview

  1. Start the experiment by adding doses of amaranth dye to the beaker system.
  2. Take samples from the central and tissue compartment beakers.
  3. Measure the absorbance of the samples using a spectrophotometer.
  4. Plot the time course of absorbance while the experiment is being performed,
  5. Construct a standard curve relating absorbance to amaranth dye concentrations on two occasions.
  6. 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