Dear All, I’m asked to compare the results from an NLME 2-cmpt analyis of steady-state data with a 19-43 day half-life. I used the reparamiterization from my 1994 NONMEM User’s Guide, appendix 2, which indicated I should use K10=Cl/V from the cerntral compartment. I followed this with the standard ln(2)/K10=t1/2. My results differ from 21 days for the NLME to 30 days for the NCA. Since the CL values are dead on, that suggests that the V term is inadequately being estimated by my reparmeterization. What is the proper reparmeterization to estimate the secondary paramter K10? 4-Week Schedule: NLME Results V Cl K10 t12 t12-Days L L/hr 1/hr hr day Mean: 3.43 0.00483 0.001409 512.045 21.335 SD: 0.37 0.00111 0.000283 109 5 CV(%): 10.7% 23.0% 20.1% 21.4% 21.4% Median: 3.49 0.00487 0.001377 504 21 Minimum: 2.77 0.00281 0.000812 335 14 Maximum: 3.90 0.00737 0.002068 854 36 4-Week Schedule: NCA Results Vz CLss Lambda_z HLLambda_z HLLambda_z L L/hr 1/hr hr day Mean: 4.95 0.00484 0.000999 720.023 30.001 SD: 1.29 0.00110 0.000201 140 6 CV(%): 26.0% 22.8% 20.1% 19.5% 19.5% Median: 4.84 0.00476 0.000986 703 29 Minimum: 3.30 0.00290 0.000674 445 19 Maximum: 8.74 0.00738 0.001556 1028 43
Sorry, my table lost all of it’s structure. [file name=Phoenix_NLME_lambda_z_post.xlsx size=10571]Certara | Drug Development Solutions 
Jim, you’re using a ‘built-in’ 2 compartment model, right? So you can use the useful trick of Set WNL model to set up the secondary parameters for you. I “think” this illustrates the wrong assumption in your calculation, to have a slope and therefore half-life analogus to the NCA model you should be instead compare HL_lambda_z with the … secondary(Beta_hl = log(2)/Beta) But I haven’t had a chance to check this with an example set - does the reasoning sound reasonable to you since the NCA thalf comes only from the last slope? Simon
Dear Simon, Yes, it seems most reasonable. I did not know that beta was a value I could access in defining secondary parameters. Is there a list of these some where so I can scout them out for myself? Thanks, and kind regards, Jim
Secondary parameters can be defined by users in the model, the Set WNL model will write a whole bunch of them for ‘library’ models 
you can see them for this model here; 
I post the fill code for this example 2-com Extravascular Dosing Simon test(){ cfMicro(A1, Cl / V, Cl2 / V, Cl2 / V2, first = (Aa = Ka)) dosepoint(Aa, idosevar = AaDose) C = A1 / V error(CEps = 1) observe(CObs = C + CEps) stparm(Ka = tvKa * exp(nKa)) stparm(V = tvV * exp(nV)) stparm(V2 = tvV2 * exp(nV2)) stparm(Cl = tvCl * exp(nCl)) stparm(Cl2 = tvCl2 * exp(nCl2)) fixef(tvKa = c(, 1, )) fixef(tvV = c(, 1, )) fixef(tvV2 = c(, 1, )) fixef(tvCl = c(, 1, )) fixef(tvCl2 = c(, 1, )) secondary(Ke = tvCl/tvV) secondary(K12 = tvCl2/tvV) secondary(K21 = tvCl2/tvV2) secondary(Ktot = K12+K21+Ke) secondary(r1 = (Ktot^2-4K21Ke)^0.5) secondary(Alpha = (Ktot+r1)/2) secondary(Beta = (Ktot-r1)/2) secondary(Gamma = tvKa) secondary(a1 = (K21-Alpha)/(Beta-Alpha)) secondary(b1 = (K21-Beta)/(Alpha-Beta)) secondary(KaAlpha = tvKa/(tvKa-Alpha)) secondary(KaBeta = tvKa/(tvKa-Beta)) secondary(aa = KaAlphaa1) secondary(bb = KaBetab1) secondary(cc = -(aa+bb)) secondary(DoseOverVol = AaDose/tvV) secondary(A = DoseOverVolaa) secondary(B = DoseOverVolbb) secondary(C = DoseOverVolcc) secondary(AUC = DoseOverVol/Ke) secondary(Alpha_hl = log(2)/Alpha) secondary(Beta_hl = log(2)/Beta) secondary(Tmax = CalcTMax(A,Alpha, B, Beta, C, Gamma)) secondary(Cmax = Aexp(-AlphaTmax)+Bexp(-BetaTmax)+Cexp(-Gamma*Tmax)) secondary(Ke_hl = log(2)/Ke) secondary(Ka_hl = log(2)/tvKa) ranef(diag(nV, nCl, nKa, nV2, nCl2) = c(1, 1, 1, 1, 1)) }
Whoa! I did not realize that option was available. Set WNL is a check box I never examined! Major help with something I’ve been struggling with for the past couple of years. I figured it had to be documented somewhere but I could not find it anywhere. Let me buy you a pint!
yes it saves me having to pull out reference books and re-arrange formulas all the time. Any good Pale Ales in Texas? or are you in Raleigh now?
Yes, I now hale from the Republic of Texas and located in Austin. I wouldn’t know about the pale ales but my son seems to have found some he likes. I’m more into the Bock lagers. One last question on the secondary parameters. I’m getting a full complement of statistics on all of the parameters excet for Tinf. Here I am missing the stdeff and CV% but getting all of the others. Any ideas why this might me happening. Individual figures confirm the program is recognizing the infusion length corrects as I have a sample at the start and end of the infusion. Kind regards, Jim