Bioequivalence and Bioavailability Forum

Hi Thalita,

If you do not have iv data for your subjects and you still want to get Fabs (fraction cumulative absorption in %) and then do Levy plots, I think probably you can do the following:

1. fit your data with one-compartment PK model, to get Ka, Kel & Vd;
   
2. use obtained 'Kel' to calculate Fabs (R codes as follows);
   
3. plot Fabs vs. FRD (from your dissolution profiles, varied pH) and get Levy plots.

In this case, you do not need iv data and no more IVIVC or Wagner-Nelson. However, I am not sure if this is what you want.

❝ ... I just tried to calculate Fabs based on Wagner Nelson equation, but the values ​​of Fabs were higher than 1. The Kel is too little. On my work group we have a study that used same in vivo data with GastroPlus and establish the correlation based on one-compartment model, because we do not have intravenous data.

R codes
for (j in 1:length(W.split)){  ### 'W.split' contains in-vivo data for all subj., j = # of subj.
  auc<- 0;Ft<- 0;Fabs<- 0
  for(i in 2:length(W.split[[j]][["time"]])){
# calculate AUC for each time point
  auc[i]<- (W.split[[j]][["time"]][i]-W.split[[j]][["time"]][i-1])*(W.split[[j]][["conc.obs"]][i]+W.split[[j]][["conc.obs"]][i-1])* 0.5
  auc[i]<- auc[i]+auc[i-1] 
# calculate F(t): fraction of absorption at time t
  Ft[i]<-W.split[[j]][["conc.obs"]][i]+kel*auc[i]}
# calculate AUC (0~INF)
  auc.infinity<-W.split[[j]][["conc.obs"]][length(W.split[[j]][["conc.obs"]])]/kel
  aucINF<-auc[length(W.split[[j]][["conc.obs"]])]+auc.infinity
# calculate Fabs(t): cumulative absorption fractions at time t
  Fabs<- 0
  for(i in 2:length(W.split[[j]][["time"]])) Fabs[i]<-(Ft[i]/(kel*aucINF))*100