Microconstant model Interconversion clearance model Table 34.1 Paramete「estimates of the micro-constant and interconversion clearance models WRSS in Table 34.1 denotes the weighted residual sum of squares. Parameter estimates are shown in Figure 34.1 and Table 34. The observed and model-predicted plasma concentrations, and the final Interpretation of results and conclusions The initial parameter estimates selected diffcεred a littleįrom the values used to gener따C the data. Procedures involved in obtaining initial parameter estimates, AUC, MRT,Īnd so on for a system of revεrsible processes are covered in depth in EblingĪnd Jusko. Pharmac。kinetic and Pharmacodynamic Data Analys is ‘ 」 Ζ” is the concentration of the monohydrate. Where κ, ζ’” Iη”” C/111 and Cl111d arε the volume, ζoncentration, input rate,Ĭlearance and inter-conversion clearancε of the monohydrate respectively. The reversal rate for conversion of the monohydrate to cisplatin is Monohydrate occurs with a rate constant derived according to Equation Where VP' CP' Iη/μ Clp and Clpd are the volume, concentration, input rate,Ĭoncentration of [ he monohydratε. That takes account of such a split inf] ut rate and clearance are shown in 「 Pharmacokinetic and Pharmacodynamic Data Analysis PK34 To estimate the disposition and interconversion parameters of the two compounds.Objectives To implement a set of differential equations mimicking reversible metabolism We have also chosen to describe thε εquilibrium process in vivo berween cisplatin and its monohydrate complex by means of rwo clearance rates. Thus, the input rate can be split into cisplatin infusion ratε Iη and monohydra[ e infusion rate In,
In an infusion solution of cisplatin, equilibrium is established berween cisplatin and its monohydratε complex.
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This exercise demonstrates how to implement the equations for this model into a program. This information was then used to obtain initial parameter estimates for a model of reversible metabolism. The aim of this exercise is to demonstrate how to implement a system of differential equations describing reversible metabolism.ĭata were taken from thε li〔eraturε on cisplatin kinetics (Andersson (1995]) and used [ O generate synthetic concentr따ion-time values for cisplatin p and its monohydrate m. Reversible metabolism, cisplatin, monohydrate, multiple compartment Introduction