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The Effect of Anesthetic Regimens on Intestinal Absorption of Passively Absorbed Drugs in Rats

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Abstract

Purpose

Different anesthetic regimens are used during single pass intestinal perfusion (SPIP) experiments for the study of intestinal drug absorption in rats. We examined the ketamine/xylazine anesthetic combination to evaluate its influence on drug absorption compared to older regimens. Additionally, we examined whether supplementary analgesia has any effect on drug absorption and the effect of the different anesthetic regimens on induction time and stress response.

Methods

Rats were anesthetized using four different anesthetic regimens; ketamine/midazolam, pentobarbital, ketamine/xylazine and ketamine/xylazine/butorphanol. Three model drugs were administered to rat intestines and Peff was calculated. Stress response was evaluated by quantifying blood corticosterone levels and induction time was recorded.

Results

We found absorption under pentobarbital to be higher or similar to absorption under ketamine/midazolam. These results partly correlate with past literature data. Ketamine/xylazine was found to give similar or higher Peff compared to pentobarbital and ketamine/midazolam. Addition of butorphanol did not affect absorption and reduced induction time and stress.

Conclusions

In studies of intestinal drug absorption, the ketamine/xylazine combination is superior to other anesthetic regimens as it is more convenient and seems to affect absorption to a lesser extent. Addition of butorphanol is highly recommended as it did not affect absorption but led to a more effective and less stress inducing experiment.

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Abbreviations

CV:

Coefficient of variation

ESI:

Electrospray ionization

K/M:

Ketamine/midazolam

K/X:

Ketamine/xylazine

K/X/B:

Ketamine/xylazine/butorphanol

P:

Pentobarbital

Peff :

Effective permeability

SD:

Standard deviation

SEM:

Standard error of the mean

SPIP:

Single Pass Intestinal Perfusion

UPLC-MS:

Ultra performance liquid chromatography - mass spectrometry

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Authors and Affiliations

  1. Department of Organic Chemistry, Israel Institute for Biological Research, P.O.B 19, 7410001, Ness-Ziona, Israel

    Sigal Saphier, Ada Wenger & Michael Goldvaser

  2. Department of Pharmacology, Israel Institute for Biological Research, P.O.B 19, 7410001, Ness-Ziona, Israel

    Guy Yacov & Shahaf Katalan

  3. Department of Applied Mathematics, Israel Institute for Biological Research, P.O.B 19, 7410001 Ness-Ziona, Israel

    Ziv Klausner

  4. Veterinary Center for Preclinical Research, Israel Institute for Biological Research, P.O.B 19, 7410001 Ness-Ziona, Israel

    Amir Rosner

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  1. Sigal Saphier
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Saphier, S., Yacov, G., Wenger, A. et al. The Effect of Anesthetic Regimens on Intestinal Absorption of Passively Absorbed Drugs in Rats. Pharm Res 37, 87 (2020). https://doi.org/10.1007/s11095-020-02809-9

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