• Journal of Pharmaceutical Investigation
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• 제36권6호
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• pp.405-411
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• 2006

Epinastine is an antiallergic drug effective for bronchial asthma, allergic rhinitis, urticaria and dermatitis. Epinastine is topically active, direct H1-receptor antagonist and an inhibitor of the release of histamine from the mast cell. The purpose of the present study was to evaluate the bioequivalence of two epinastine hydrochloride tablets, Alesion Tablet (Boehringer Ingelheim Korea Ltd.) and S-napine tablet 10 mg(Sam Chun Dang Pharm. Co., Ltd), according to the guidelines of the Korea Food and Drug Administration(KFDA). The release of epinastine from the two epinastine formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media(pH 1.2, 4.0, 6.8 buffer solution and water). Twenty six healthy male subjects, $23.35{\pm}1.57$ years in age and $66.29{\pm}10.61kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two tablets containing 20 mg as epinastine hydrochloride was orally administered, blood was taken at predetermined time intervals and the concentrations of epinastine in serum were determined using HPLC with UV detector. The dissolution profiles of two formulations were similar at all dissolution media. In addition, the pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t.\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, Alesion tablet, were 1.50, 1.46 and -13.48% for $AUC_t,\;C_{max}\;and\;T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25(e.g., log 0.95$\sim$log 1.12 and log 0.93$\sim$log 1.10 for $AUC_t\;and\;C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating S-napine tablet 10 mg was bioequivalent to Alesion tablet.

• 대한화학회지
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• 제54권4호
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• pp.447-450
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• 2010

본 연구에서는 제2세대 항히스타민제인 에피나스틴 염산염의 대량합성을 위한 개선된 합성법을 제시하였다. 기존의 합성경로는 중요중간체인 aminomethyl 유도체를 합성하기 위해 독성이 매우 강한 phosgene과 sodium cyanide 및 폭발 위험성이 있으며 고가인 aluminum chloride와 lithium aluminum hydride 등 대량합성에 부적합한 위험물질을 사용해야 하는 단점이 있다. 이를 해결하기 위해서 먼저 phthalimidomethyl 유도체를 합성한 다음 염산 또는 methylhydrazine을 사용하여 phthalyl 기를 용이하게 제거하는 방법으로 aminomethyl 유도체를 합성하였고, 이 과정에서 위험물질 및 고가의 반응물의 사용을 배제하였는바 이는 산업상 매우 유용한 개량방법이라 하겠다.

• 대한화학회지
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• 제64권2호
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• pp.79-83
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• 2020

A novel pharmacophore with epinastine (1) and NSAID moieties (2-5) was designed by molecular hybridization approach. The hybrid compounds 6-9 were synthesized by EDCI/HOBt or HATU-mediated coupling of 1 with salicylic acid (2), mefenamic acid (3), indomethacin (4) and naproxen (5), respectively, and were assessed for their inhibitory effect against NO production in LPS-induced RAW-264.7 macrophages in vitro. The Hybrids were found to exhibit significant NO production inhibitory effects with half-maximal inhibitory concentration (IC₅₀) values ranging in between 15.96 ± 1.32 and 36.68 ± 2.53 μM and were non-cytotoxic to macrophages. Comparing the inhibition concentration (IC₅₀), cytotoxicity concentration (CC₅₀) and in vitro efficacy index (iEI), 6 (IC₅₀ = 17.97 ± 1.92 μM; iEI = 11.13) and 9 (IC₅₀ = 15.96 ± 1.32 μM; iEI = 12.53) were better suited than other hybrids as well as their parent compound. Our findings signify that hybrids 6 and 9 may serve as platforms for continued investigations for the development of more efficient anti-inflammatory agents.