A freely moving and behaving rat model for the chronic and simultaneous study of drug pharmacokinetics (blood) and neuropharmacokinetics (cerebrospinal fluid): Hematological and biochemical characterization and kinetic evaluation using carbamazepine

作者: Philip N. Patsalos , Mohammed S. Alavijeh , Jun'ichi Semba , Yvette I. Lolin

DOI: 10.1016/1056-8719(92)90061-5

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摘要: Abstract A freely moving and behaving rat model for the chronic simultaneous study of drug pharmacokinetics (blood) neuropharmacokinetics [cerebrospinal fluid (CSF)] is described. The blood (jugular vein) CSF (cisterna magna) catheters employed are simple, reliable, inexpensive. catheter was made soft flexible Silastic tubing sealed with heparin. consisted intersliding polythene interlocking tubing, which allowed maneuverability within cisternal magna space thus prolonging patency studies. Both were well tolerated by animals, postoperative success rate 80%–100%; after 8 days 80%–85% still patent. Using a sampling protocol considered suitable kinetic studies, we determined numerous biochemical hematological parameters compared them those values obtained postsurgically in control rats. parameter changes associated did not affect kinetics commonly prescribed antiepileptic carbamazepine its primary pharmacologically active metabolite carbamazepine-10, 11-epoxide. Therefore, can be used to interrelationship between at central peripheral sites mechanism(s) action.

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