Effect of route of administration on the pharmacokinetics and toxicokinetics of cinnarizine in dogs

Bao-qiu, LI; Yang, Guiqin; Fang, Shi-hong; Gao, Ji-you; Gu, Fang-min; Dong, Xin; Zhang, Jianxin; Wang, Yong

doi:10.1016/j.ejps.2010.03.013

Cited by 13 publications

(3 citation statements)

References 22 publications

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“…After oral administration, cinnarizine is rapidly absorbed ( T max⁡ = 2–4 h) from gastrointestinal tract, with an absorption window in upper gastrointestinal tract [ 5 ]. On repetitive dosing in healthy human, accumulation of cinnarizine occurs due to its pharmacokinetic properties [ 6 ]. The drug can cross the blood-brain barrier by simple diffusion, due to weakly basic and lipophilic [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in Delivery Systems and Therapeutics of Cinnarizine: A Poorly Water Soluble Drug with Absorption Window in Stomach

Raghuvanshi

Pathak

2014

Journal of Drug Delivery

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Low solubility causing low dissolution in gastrointestinal tract is the major problem for drugs meant for systemic action after oral administration, like cinnarizine. Pharmaceutical products of cinnarizine are commercialized globally as immediate release preparations presenting low absorption with low and erratic bioavailability. Approaches to enhance bioavailability are widely cited in the literature. An attempt has been made to review the bioavailability complications and clinical therapeutics of poorly water soluble drug: cinnarizine. The interest of writing this paper is to summarize the pharmacokinetic limitations of drug with special focus on strategies to improvise bioavailability along with effectiveness of novel dosage forms to circumvent the obstacle. The paper provides insight to the approaches to overcome low and erratic bioavailability of cinnarizine by cyclodextrin complexes and novel dosage forms: self-nanoemulsifying systems and buoyant microparticulates. Nanoformulations need to systematically explored in future, for their new clinical role in prophylaxis of migraine attacks in children. Clinical reports have affirmed the role of cinnarizine in migraine prophylaxis. Research needs to be dedicated to develop dosage forms for efficacious bioavailability and drug directly to brain.

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Section: Introductionmentioning

confidence: 99%

Recent Advances in Delivery Systems and Therapeutics of Cinnarizine: A Poorly Water Soluble Drug with Absorption Window in Stomach

Raghuvanshi

Pathak

2014

Journal of Drug Delivery

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“…It is administrated intratracheally, intraperitoneally or intravenously, and contains a pivaloyl ester 46,47 that likely causes FAP inhibition by transesterification of the active site serine. Depending on a concentration of sivelestat in human plasma [48][49][50] , there might be a risk of interference with FAP-targeting compounds administered simultaneously. The last subgroup of Group I compounds consists of drugs targeting FAP's closest homolog, DPP-IV, to treat type 2 diabetes [51][52][53] .…”

Section: The Most Potent Fda-approved Compounds Inhibiting Fap (Group I)mentioning

confidence: 99%

Sensitive quantification of fibroblast activation protein and high-throughput screening for inhibition by FDA-approved compounds

Čermáková,

Šimková,

Wichterle

et al. 2024

Preprint

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Fibroblast activation protein (FAP) has been extensively studied as a cancer biomarker for decades. Recently, small-molecule FAP inhibitors have been widely adopted as a targeting moiety of experimental theranostic radiotracers. Here we present a fast qPCR-based analytical method allowing FAP inhibition screening in a high-throughput regime. In order to identify clinically relevant compounds that might interfere with FAP-targeted approaches, we focused on the library of FDA-approved drugs. Using theDNA-linkedInhibitorAntibodyAssay (DIANA), we tested a library of 2,667 compounds within just few hours and identified numerous FDA-approved drugs as novel FAP inhibitors. Notably, prodrugs of cephalosporin antibiotics, reverse-transcriptase inhibitors, and one elastase inhibitor were the most potent FAP inhibitors in our dataset. In addition, by employing FAP DIANA in quantification mode, we were able to determine FAP concentrations in human plasma samples. Together, our work expands the repertoire of FAP inhibitors, underscores the potential interference of co-administered drugs with FAP-targeting strategies, and presents a sensitive and low-consumption ELISA alternative for FAP quantification with a detection limit of 50 pg/ml.Graphical abstract

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“…Despite the long half-life cinnarizine has, the frequency of administration is three to four times a day as a result of its limited solubility as the GI fluid is not able to dissolve such a high amount of the drug all at once. Cinnarizine is well absorbed in the upper gastrointestinal tract (GIT) due to its high lipophilic properties; however, the same properties limit the solubility and the readiness for absorption as a limiting step [4]. Therefore, enhancing the drug solubility and dissolution profile may be the key to improving the pharmacokinetic properties of the therapeutic agent.…”

Section: Introductionmentioning

confidence: 99%

Lyophilization-free proliposomes for sustained release oral delivery of hydrophobic drug (cinnarazine): a comparative study

Abed

Mulkala

Sharif

et al. 2021

Pharmaceutical Technology in Hospital Pharmacy

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Objectives Cinnarizine is used for the treatment of vestibular disorders. However, its poor solubility limits its clinical uses due to many challenges. Liposomes were utilised to improve the release profile of many poorly soluble drugs. However, liposomes face many stability challenges during the storage period. This study aims to develop proliposomes designed for the oral delivery of cinnarizine with enhanced stability characteristics. Methods Three cinnarizine entrapping Proliposomal formulations were prepared with different ingredients and compared with their liposomal counterparts. Both vesicular approaches were characterised for their particle size, encapsulation efficiency, drug release and stability. Results The proliposomes were superior to liposomes in their stability and release profiles. Although no significant changes were noticed between the encapsulation efficiency percentage of the liposomal and proliposomal formulations on the day of preparation, storing the formulations for two weeks ended up with significant leakage of the drug from liposomes (p < 0.05) due to stability issues, but not in proliposomes. Moreover, the proliposomes released 100% of cinnarizine throughout the dissolution experiment in gastric fluid in comparison with the total released drug of 70% from the liposomes. Conclusions Proliposomes provided a successful approach to deliver lipophilic drugs orally to improve their pharmacokinetic properties by converting their crystalline nature into more amorphous agents.

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Effect of route of administration on the pharmacokinetics and toxicokinetics of cinnarizine in dogs

Cited by 13 publications

References 22 publications

Recent Advances in Delivery Systems and Therapeutics of Cinnarizine: A Poorly Water Soluble Drug with Absorption Window in Stomach

Recent Advances in Delivery Systems and Therapeutics of Cinnarizine: A Poorly Water Soluble Drug with Absorption Window in Stomach

Sensitive quantification of fibroblast activation protein and high-throughput screening for inhibition by FDA-approved compounds

Lyophilization-free proliposomes for sustained release oral delivery of hydrophobic drug (cinnarazine): a comparative study

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