Dears Leonid and Saeheum, First of all, thank you for your suggestions, they are very useful and cleared up some queries I had. Leonid, regarding your question about measurement of free or total ligand concentration, in this study we only measured the free ligand concentration.
Thank so much, Regards, Niurys 2019-04-23 12:00 GMT-05:00, Leonid Gibiansky <lgibian...@quantpharm.com>: > The code will work as written (if you add ENDIF after TVVM = THETA (6), > and define all parameters CL, V1, Q, V2, KINT, ...) but mechanistically, > this is not a good idea to have two models for two dose levels. You may > want to try QSS model with non-constant Rtot (MM model is usually good > when Rtot is low, while QSS is good when Rtot has accumulation, so may > be this is why you see MM model at low doses and QSS at high doses). > > Also, what is measured, is it free or total concentration? This part of > the code was not shown, and it depends on the assay (for QSS part of the > model). > > Thanks > Leonid > > > On 4/23/2019 8:34 AM, Niurys.CS wrote: >> Dear All, >> >> I'm working on the population pharmacokinetics of a mAb, in this study >> 4 dose levels (50, 100, 200 and 400 mg) were evaluated. I tested >> different models, but none of them fit well; that's why I decided to >> find for each dose level the best model. I found the two lower dose >> levels fitted to Michaelis Menten + CL linear model and the two higher >> dose levels fitted to QSS Rtot model. >> I think if I use this code, I'll find the best model for my data, so I >> appreaciate your suggestions: >> >> $PK >> >> TVCL= THETA(1) >> TVV1= THETA(2) >> TVQ = THETA(3) >> TVV2 = THETA (4) >> >> TVKM = 0 >> TVVM = 0 >> >> IF(DOS.LT.200) THEN >> TVKM = THETA (5) >> TVVM = THETA (6) >> >> TVKSS = 0 >> TVKINT = 0 >> TVKDEG = 0 >> TVRMAX = 0 >> >> IF(DOS.GT.100) THEN >> >> TVKSS = THETA (7) >> TVKKINT = THETA(8) >> TVRMAX = THETA(9) >> >> ENDIF >> >> >> K = CL/V1 >> K12 = Q/V1 >> K21 = Q/V2 >> S1 = V1 >> >> ;---------------------------------- >> $DES >> >> CONC=0.5*(A(1)/V1-RMAX-KSS)+0.5*SQRT((A(1)/V1-RMAX-KSS)**2+4*KSS*A(1)/V1) >> >> DADT(1) = >> -(K+K12)*CONC*V1+K21*A(2)-KINT*RMAX*CONC*V1/(KSS+CONC)-VM*CONC*V1/(KM+CONC) >> DADT(2) = K12*CONC*V1-K21*A(2) >> >> >> Thank you, >> >> Regards, >> Niurys de Castro >> > -- MSc Niurys de Castro Suárez Profesor Asistente Farmacometría Investigador Agregado Departamento Farmacia Instituto de Farmacia y Alimentos, Universidad de La Habana Cuba "Una estrella brilla en la hora de nuestro encuentro"
