• Journal of Pharmaceutical Investigation
• /
• 제27권3호
• /
• pp.219-223
• /
• 1997

Terfenadine, antihistaminic drug, is poorly soluble in water. The purpose of this study is to investigate the possibility of using $terfenadine-{\beta}-cyclodextrin$ inclusion compound, instead of terfenadine, as the active substance of solid dosage form by improving the solubility, dissolution and anti-histaminic activity of terfenadine. The solubility and binding characteristics of $terfenadine-{\beta}-cyclodextrin$ complex in pH $1.2{\sim}6.8$ were investigated. Furthermore, the preparing method of $terfenadine-{\beta}-\;cyclodextrin$ inclusion compound was setting up and its physico-chemical characteristics such as DSC curve, solubility, dissolution and anti-histaminic activity were investigated. In conclusion, the solubility of terfenadine was increasing ${\beta}-cyclodextrin$ and with the decreasing pH. $Terfenadine-{\beta}-cyclodextrin$ inclusion compound, whose yield is almost 100%, was prepared by neutralization method. This inclusion compound was 200-times as soluble as terfenadine in pH 1.2-6.8. In addition, it had the faster dissolution and anti-histaminic activity than terfenadine. Therefore, it is used to the active substance of solid dosage form such as tablet and capsule in stead of terfenadine.

• Journal of Pharmaceutical Investigation
• /
• 제27권3호
• /
• pp.213-217
• /
• 1997

The present sustained-release terfenadine-pseudoephedrine HCl dosage form was the core tablet composed of outer (fast-release) layer containing 60 mg of terfenadine and l0mg of pseudoephedrine HCl, and inner (sustained-release) layer containing 110 mg of pseudoephedrine HCl. The purpose of this study was to investigate the possibility of formulating the terfenadine-pseudoephedrine HCl double-layered tablet which was bioequivalent to the core tablet. Its sustained-release and fast-release layer were formulated with disintegrating agents and polymers, respectively, varying with their kinds and amounts. The comparative dissolution test of double-layered and core tablet was carried out at pH 1.2, 4.0 and 6.8, leading to select composite of double-layered tablet whose dissolution pattern was similar to that of core tablet. It was composed of fast-release layer containing 60mg of terfenadine. 10 mg of pseudoephedrine HCl, sodium bicarbonate, microcrystalline cellulose and sodium starch glycolate, and sustained-release layer containing 110 mg of pseudoephedrine HCl and ethylcellulose/hydroxypropyl methylcellulose) (110/30 mg/tablet).

• 한국임상수의학회지
• /
• 제19권2호
• /
• pp.186-190
• /
• 2002

아토피성 피부염은 면역계재성 피부질환으로 소양증이 주요 증상이며 이의 치료가 필수적이다. 따라서 개에서 제2세대 항히스타민제의 임상적용을 위해 피부에 히스타민에 의해 유발된 팽진과 발적에 대한 loratadine, cetirizine과 terfenadine의억제 효과를 비교하였다. 3종의 항히스타민제는 대조군에 비해 매우 유의하게 발적반응을 억제하였으며(p<0.01) cetirizine이 다른 제제에 비해 높은 억제효과를 보였다. 3종의 항히스타민제는 팽진 반응을 억제하는 효과를 보였으며 loratadine의 억제효과가 일정하며 지속적이었다. 따라서 제 2세대 항히스타민제인 loratadine과 cetirizine은 개에서 아토피성 피부염의 소양증 치료에 적용할 수 있는 항히스타민제로 사료된다. 특히 스테로이드제제를 대체할 수 있는 치료효과를 보일 것으로 판단된다.

• Journal of Pharmaceutical Investigation
• /
• 제35권6호
• /
• pp.437-443
• /
• 2005

A rapid, selective and sensitive reversed-phase HPLC method for the determination of a major metabolite of terfenadine, fexofenadine, in human serum was developed, validated, and applied to the pharmacokinetic study of terfenadine. Fexofenadine and internal standard, haloperidol were extracted from human serum by liquid-liquid extraction with acetonitrile and analyzed on a $Symmetry^{TM}$ C8 column with the mobile phase of 1% triethylamine phosphate (pH 3.7)-acetonitrile (67:33, v/v, adjusted to pH 5.6 with triethylamine). Detection wavelength of 230 nm for excitation, 280 nm for emission and flow rate of 1.0 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^{3}$ factorial design using a fixed fexofenadine concentration (50 ng/mL) with respect to its peak area and retention time. In addition, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of 10-500 ng/mL with correlation coefficients greater than 0.999. The lower limit of quantification using 0.5 mL of serum was 10 ng/mL, which was sensitive enough for the pharmacokinetic studies of terfenadine. The overall accuracy of the quality control samples ranged from 95.70 to 114.58% for fexofenadine with overall precision (% C.V.) being 3.53-14.39%. The relative mean recovery of fexofenadine for human serum was 90.17%. Stability studies (freeze-thaw, short-term, extracted serum sample and stock solution) showed that fexofenadine was stable during storage, or during the assay procedure in human serum. However, the storage at $-70^{\circ}C$ for 4 weeks showed that fexofenadine was not stable. The peak area and retention time of fexofenadine were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of fexofenadine in human serum samples for the pharmacokinetic studies of orally administered Tafedine tablet (60 mg as terfenadine) at three different laboratories, demonstrating the suitability of the method.

• 대한임상약리학회:학술대회논문집
• /
• 대한임상약리학회 1997년도 정기총회 및 추계학술대회
• /
• pp.52-52
• /
• 1997

• 생명과학회지
• /
• 제21권11호
• /
• pp.1558-1564
• /
• 2011

CYP2J2는 치료약물 및 아라키돈산과 같은 내인성 화합물의 대사에 중요한 역할을 수행하고 있는 효소이다. 최근, CYP2J2 단백질이 인체 종양 조직이나 종양 세포주에 과발현되어 있고, CYP2J2 효소의 작용에 의해 생성된 에폭시에이코사트리에논산(EETs)이 세포사멸을 방지한다는 것이 보고되었다. 본 연구는 시판중인 약물 120종을 대상으로 시토크롬 2J2 동종효소에 저해능을 가지는 화합물을 발굴하고자 하였다. 인체 간 마이크로솜 시료에 아스테미졸과 NADPH 재생성계 및 약물(50 ${\mu}M$)을 첨가한 후 15분간 반응시켜 생성된 대사물을 LC/MS/MS를 이용하여 분석하여 시토크롬 2J2 동종효소 활성의 변화를 평가하였다. 그 결과 할로페리돌, 터페나딘, 아리피프라졸, 미코나졸의 순으로 CYP2J2 효소 활성 저해능을 보였다. 미코나졸은 CYP2J2에 의해 매개되는 에바스틴($IC_{50}$=11.2 ${\mu}M$) 및 터페나딘($IC_{50}$=2.2 ${\mu}M$) 대사를 강력하게 저해하였다. 터페나딘 또한 CYP2J2 매개 에바스틴 대사를 농도 의존적으로 저해하였다($IC_{50}$=13.6 ${\mu}M$). 향후, 이들 약물을 대상으로 한 항암 활성 평가가 필요할 것으로 판단된다.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2000년도 춘계총회 및 학술대회
• /
• pp.206.3-207
• /
• 2000

• Natural Product Sciences
• /
• 제12권1호
• /
• pp.55-61
• /
• 2006

A description of simple, isocratic and precise reversed phase HPLC methods is given for simultaneous quantification of pholcodine and ephedrine hydrochloride together with either carbinoxamine maleate or terfenadine in antitussive-antihistaminic oral pharmaceutical formulations. Separations were carried out on X-Terra and symmetry shield C18 column $(250\;{\times}\;4.6\;mm,\;5\;{\mu}m)$. The used isocratic elution systems were either $0.02\;M\;KH_2PO_4-acetonitrile$ in the ratio of 75 : 25 and pH adjusted to 7.70 with orthophosphoric acid or sodium hydroxide, for syrup (method A), or 0.02 octanesulphonic acid sodium salt solution-acetonitrile-acetic acid in the ratio of 75 : 25 : 0.5 for suspension (method B). The elution of both mixtures was achieved with a flow rate of 1 ml/min. Detection was carried out by UV absorbance at wavelengths of 220 and 250 nm for syrup and suspension, respectively. The quantification of the components in synthetic mixtures and actual syrup and suspension were calculated using the internal standard technique with metoclopramide HCl and codeine phosphate as internal standards (IS), respectively. The methods, for both mixtures, were validated and met all the requirements for the quality control analysis recommended by FDA and ICH.

• Toxicological Research
• /
• 제30권1호
• /
• pp.33-38
• /
• 2014

The human cytochrome P450 2J2 catalyzes an epoxygenase reaction to oxidize various fatty acids including arachidonic acid. In this study, three recombinant enzyme constructs of P450 2J2 were heterologously expressed in Escherichia coli and their P450 proteins were successfully purified using a $Ni^{2+}$-NTA affinity column. Deletion of 34 amino acid residues in N-terminus of P450 2J2 enzyme (2J2-D) produced the soluble enzyme located in the cytosolic fraction. The enzymatic analysis of this truncated protein indicated the typical spectral characteristics and functional properties of P450 2J2 enzyme. P450 2J2-D enzymes from soluble fraction catalyzed the oxidation reaction of terfenadine to the hydroxylated product. However, P450 2J2-D enzymes from membrane fraction did not support the P450 oxidation reaction although it displayed the characteristic CO-binding spectrum of P450. Our finding of these features in the N-terminal modified P450 2J2 enzyme could help understand the biological functions and the metabolic roles of P450 2J2 enzyme and make the crystallographic analysis of the P450 2J2 structure feasible for future studies.

• Mass Spectrometry Letters
• /
• 제11권4호
• /
• pp.113-117
• /
• 2020

Cytochrome P450 2J2 (CYP2J2) is a member of the cytochrome P450 superfamily, and is known to be arachidonic acid epoxygenase that mediates the formation of four bioactive regioisomers of epoxyeicosatrienoic acids (EETs). CYP2J2 is also involved in the metabolism of drugs such as albendazole, astemizole, danazol, ebastine, and terfenadine. CYP2J2 is highly expressed in the heart and cancer tissues. In this study, the inhibitory potential of ten natural products against CYP2J2 activity was evaluated using human liver microsomes and tandem mass spectrometry. Among them, bilobetin, which is a kind of biflavonoid, exhibits a strong inhibitory effect against the CYP2J2-mediated astemizole O-demethylation (IC50 = 0.73 μM) and terfenadine hydroxylation (IC50 = 0.89 μM). This result suggests that bilobetin can be used as strong CYP2J2 inhibitor in drug metabolism study.