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Alex ☆ Austria, 2015-04-14 14:48 (3293 d 12:05 ago) Posting: # 14682 Views: 4,932 |
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Dear friends! I am involved in the planing phase of a repeated dose TK study (pre-clincal) in which drug is administered by infusion and I am wondering whether there is a conflict regarding zero-order absorption processes and linear kinetics IF one can assume a constant infusion interval (for a given dose range)? I want to know if it is valid to play around with different simulated scenarios (different doses, different dosing intervals, ...) on the assumption of linear kinetics AND a constant infusion interval... Thanks a lot, as always... Alex |
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Helmut ★★★   Vienna, Austria, 2015-04-14 16:38 (3293 d 10:15 ago) @ Alex Posting: # 14684 Views: 3,883 |
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Hi Alex, you can assume anything and will know after the experiment.  Theoretically infusion rates matter. It might be that with a fast infusion rate you saturate the metabolizing enzyme(s) (high Cmax) and with a slow one (low Cmax) not. You could expect a slower elimination in the former case. However, unless you torture the enzymes in such a way that the elimination switches at high concentrations to zero-order (like C2H5OH) you could still expect ~equal AUCs (=linear PK). Personally I don’t think you should be too worried about infusions. Such effects are more likely if comparing very fast releasing oral formulations with MR. — Dif-tor heh smusma 🖖🏼 Довге життя Україна! ![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png) Helmut Schütz ![[image]](https://static.bebac.at/img/CC by.png) The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
Ing. Helmut Schütz