## No CO, please [🇷 for BE/BA]

Hi Weidson,

❝ Thank you very much for answer!!!

Welcome.

❝ It was very complete!!!

No, it wasn’t. Just realized that I worked with the source-code of method.A(), where the columns are in lower case (and not in upper case like in your data set). Corrected in my post above. Sorry.

❝ And here, the new results

#########################################################################

❝ Type III Analysis of Variance Table

❝

❝ Response: log(Cmax)

 ❝                   Df   Sum Sq Mean Sq F value   Pr(>F)    ❝ Sequence           1   1.3253 1.32531 0.27224 0.604233    ❝ Period             3   3.5824 1.19413 2.19909 0.090673 .  ❝ Treatment          1   2.7923 2.79228 5.14222 0.024818 *  ❝ Sequence:Subject  48 233.6721 4.86817 8.96514  < 2e-16 ***❝ Residuals        146  79.2796 0.54301                     ❝ ---

❝ Signif. codes:  0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1

Perfect.

One last doubt: How can we include at function lme() a term for carryover first-order effect (keeping the sequence effect in the model)? We have many DF for estimate this effect, so I presume that it can be estimated to replicate designs as this our example!!! How and how many columns should we have in the dataset to estimate the first-order carryover effect?

❝ This test can be useful when we are working with auto-inducers drugs (I read your article and I like very much).

Nope. See there again and think about the carbamazepine example.* I had a straightforward induction model behind, i.e., $$\small{\textrm{I}(t)=1\,(-\exp(-\alpha\cdot t)\,)}$$. With $$\small{\alpha=1}$$ we have practically complete induction (99.48%) on day 5 (Clearance going from 1.35 down to 5.84). Clearly that’s nonlinear and even if we would manage to introduce 1st, 2nd, nth-order carryover in the model, it has no relationship to the real world.

❝ At Phoenix WinNonlin this can be make creating two collumns named "Carry" and "Over". […]

Never did that and never will.

❝ How would be this parametrization at function lme at R software?

No idea.

• Tóthfálusi L, Endrényi. Approvable generic carbamazepine formulations may not be bioequivalent in target patient populations. Int J Clin Pharmacol Ther. 2013; 51(6): 525–8. doi:10.5414/CP201845.

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