*2.9. Pharmacokinetic Analysis*

Pharmacokinetic analyses were conducted in R [17]. First, a non-compartmental analysis was performed. Assumptions were: (i) dose was calculated by concentration in the reservoir x volume (Figure 1a(3)); (ii) area under the concentration curve (AUC) 0–48 h lasted until 48 h and AUC 48–96 h until the end of the experiment; (iii) for the concentration between 48–96 h the unmeasured concentrations were not considered. Afterwards, interval AUCs were calculated. For 0–48 h, the AUC was calculated from 0.0001 h (start of the experiment) to the end of the 1st cycle; for 48–96 h, the AUC was calculated from the time "end of the 1st cycle" to "end of the 2nd cycle". However, the end of the 2nd cycle varied, since in some experiments, the last concentrations could not be measured. The maximum concentration (Cmax) was determined based on the measured concentrations; time to maximum concentration (tmax) was the corresponding time to Cmax.

#### **3. Results**
