ArticlePharmaceutical research2014
Pharmacokinetic comparison between the long-term anesthetized, short-term anesthetized and conscious rat models in nasal drug delivery.
Article in Pharmaceutical research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 11 citations in OpenAlex.
- Intranasal Diazepam Outperforms Midazolam and Lorazepam in Early Seizure Control in Pilocarpine-Induced Mice Model.Neurochemical research · 2026Article
- Significantly Increased Aqueous Solubility of Piperine via Nanoparticle Formulation Serves as the Most Critical Factor for Its Brain Uptake Enhancement.International journal of nanomedicine · 2025Article
- The development and validation of an HPLC-MS/MS method for the determination of eriocitrin in rat plasma and its application to a pharmacokinetic study.RSC advances · 2020Article
- Physiologically Based Modeling Approach to Predict Dopamine D2 Receptor Occupancy of Antipsychotics in Brain: Translation From Rat to Human.Journal of clinical pharmacology · 2019Article
- Demonstration of Direct Nose-to-Brain Transport of Unbound HIV-1 Replication Inhibitor DB213 Via Intranasal Administration by Pharmacokinetic Modeling.The AAPS journal · 2017Article
- The Role of Inhaled Loxapine in the Treatment of Acute Agitation in Patients with Psychiatric Disorders: A Clinical Review.International journal of molecular sciences · 2017Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo investigate the pharmacokinetic differences between the common nasal delivery models.
methodsIn three different rat models [long-term anesthetized (with nasal surgery), short-term anesthetized (without nasal surgery) and conscious models], tacrine and loxapine were administered via nasal, intravenous and oral routes, and the plasma pharmacokinetics were compared among different models.
resultsSystemic exposures of both drugs and their metabolites were consistently higher in long-term anesthetized model after all routes of administration in comparison to that of conscious model. Nasal bioavailabilities in long-term anesthetized model (tacrine 83%, loxapine 97%) were much higher than that in conscious model (tacrine 10%, loxapine 46%). Further studies on tacrine and its metabolites demonstrated no significant difference in t1/2 between short-term anesthetized and conscious models after all routes of administration; however, long-term anesthetized model showed significantly longer t1/2. Regarding the pharmacokinetic parameters (Cmax, Tmax, AUC, bioavailability) of tacrine and its metabolites, short-term anesthetized model resembled closer to conscious model than long-term anesthetized model.
conclusionsPlasma clearances of tacrine, loxapine, and their metabolites were much slower in the long-term anesthetized model of nasal delivery probably due to suppressed hepatic and renal clearances, while the short-term anesthetized model imposed less impact on tacrine pharmacokinetics and metabolism.
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