• Archives of Pharmacal Research
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• 제28권6호
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• pp.730-735
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• 2005

Nine polymorphic modifications of doxazosin mesylate have been obtained by recrystallization in organic solvents under variable conditions. Different polymorphs of doxazosin mesylate were characterized by powder X-ray crystallography diffractometry (PXRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TG). Transformation of Form 1 and Form 2 was not occurred in three relative humidities ($0\%$, $51\%$, and $99\%$) at 20$\pm$0.5 for 30 days.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.199-203
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• 2014

Background: Rosuvastatine, doxazosin, repaglinide and oxcarbazepin are therapeutic drugs available in the market for the treatment of different diseases. Potential to display antitumor activities has also been suggested. The aim of the current study was to evaluate their in vitro effects on some human transformed cell lines. Materials and Methods: Cytotoxicity of the four drugs was tested in MCF-7, HeLa and HepG2 cells by the neutral red assay method and also the effect of rosuvastatine and doxazosin against Ehrlich Ascities Carcinoma Cells (EACC) by trypan blue assay. Results: Rosuvastatine exerted the greatest cytotoxic effect against HepG2 cells with an $IC_{50}$ value of $58.7{\pm}69.3$; in contrast doxazosin showed least activity with $IC_{50}=104.4{\pm}115.7$. Repaglinide inhibited the growth of both HepG2 and HeLa cells with $IC_{50}$ values of $87.6{\pm}117.5$ and $89.3{\pm}119.5$, respectively. Oxcarbazepine showed a potent cytotoxicity against both HeLa ($IC_{50}=19.4{\pm}43.9$) and MCF7 cancer cells (($IC_{50}=22{\pm}35.7$).On the other hand the growth of EACC was completely inhibited by doxazosine (100% inhibition) while rosuvastatine had weak inhibitory activity (11.6%). Conclusions: The four tested drugs may have cytotoxic effects against hepatic, breast and cervical carcinoma cells; also doxazosine may inhibit the growth of endometrial cancer cells. Further investigations in animals are needed to confirm these results.

• Journal of Pharmaceutical Investigation
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• 제30권1호
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• pp.61-65
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• 2000

Doxazosin, a postsynaptic selective ${\alpha}1-adrenoceptor$ antagonist, is a potent antihypertensive agent which reduces peripheral resistance and blood pressure by vasodilatation of peripheral vessels. It is also used in the treatment of urinary obstruction by benign prostatic hypertrophy. The purpose of the present study was to evaluate the bioequivalence of two doxazosin tablets, $Cardura^{TM}$ (Pfizer Korea Ltd.) and $Cardil^{TM};$ (Kyungdong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Sixteen normal male volunteers, $24.19{\pm}2.48$ years in age and $62.41{\pm}6.66$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 2 mg of doxazosin was orally administered, blood was taken at predetermined time intervals and the concentrations of doxazosin in serum were determined with an HPLC method using spectrofluorometric detector. 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. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two tablets were -1.54%, -1.51 % and 3.42%, respectively, when calculated against the $Cardura^{TM}$ tablet. The powers $(1-{\beta})$ for $AUC_t,\;C_{max}\;and\;T_{max}$ were all more than 99.00%. Minimum detectable differences $(\Delta)$ at ${\alpha}=0.05\;and\;1-{\beta}=0.8$ were all less than 20% (e.g., 12.73%, 12.84% and 13.01% for $AUC_t,\;C_{max}\;and\;T_{max}$, respectively). The 90% confidence intervals were all within :${\pm}20%$ (e.g., $-8.97{\sim}5.90,\;-9.01{\sim}6.00\;and\;-4.16{\sim}11.05\;for\;AUC_t,\;C_{max}\;and\;T_{max},\;respectively)$. All of the above para- meters met the criteria of KFDA for bioequivalence, indicating that $Cardil^{TM}$ tablet is bioequivalent to $Cardura^{TM}$ tablet.

• 폴리머
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• 제32권4호
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• pp.322-327
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• 2008

본 연구에서 제조한 다중층 펠렛은 수팽윤성 고분자를 포함하는 시드층, 모델 약물인 독사조신을 함유한 약물층, 약물의 방출을 제어하는 다공성막 그리고 지질층으로 구성되어 있으며, 유동층 코팅 방법을 이용하여 제조하였다. 펠렛을 구성하는 각각의 층에 다양한 특성을 가지는 고분자들의 블렌딩에 따른 독사조신의 약물방출 거동을 확인하기 위하여 히드록시프로필메틸셀룰로오스(HPMC)와 에틸셀룰로오스(EC)의 양을 달리하여 약물층을 제조하였고, 셀룰로오스 아세테이트(CA)와 $Eudragit^{(R)}$ RS의 비율을 달리하여 다공성막을 제조하였다. 그리고 지질층에 의한 방출 거동을 확인하고자 피마자유의 두께를 다르게 하여 펠렛을 제조한 결과, 대략 $1500{\mu}m$의 균일한 크기를 가지는 구형의 펠렛을 얻었다. 수용액에서 용출시험을 통하여 시간에 따른 약물방출량을 확인한 결과, 약물층에 첨가된 고분자 중, EC의 비율과 다공성막에서 CA의 비율이 증가하고, 피마자유층의 두께가 두꺼워지면 약물의 방출이 감소함을 알 수 있었다. 그리고 약물방출을 제어하는데 가장 큰 역할을 하는 다공성막의 다공형성거동 역시 SEM을 통해 확인하였다.

• 한국임상약학회지
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• 제33권2호
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• pp.86-96
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• 2023

Background: Using KIDS-KAERS database (KIDS-KD) from 2016 to 2020, the aim is to investigate signals of adverse events of alpha-adrenoceptor antagonists and to present adverse events that are not included in the precautions for use when marketing approval. Methods: This study was conducted by disproportionality analysis. Data mining analysis was performed to detect signals of alpha-adrenoceptor antagonists, such as terazosin, doxazosin, alfuzosin, silodosin, and tamsulosin. The signal was defined by three criteria as proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC). Detected signals were compared with product labeling and the European Medicines Agency-Important Medical Events list. Results: Out of the total number of 408,077 reports for adverse events, 6,750 cases were reported as adverse events of alpha-adrenoceptor antagonists. Dizziness, mouth dryness, hypotension postural, and oedema peripheral are identified as common adverse events of five alpha-adrenoceptor antagonists and are typically listed on drug labels. However, new signals were detected for pneumonia, chronic obstructive airway disease, eye diseases such as glaucoma and cataracts, fracture, and ileus of tamsulosin that were not previously listed on the drug labels in Korea. Conclusions: This study identified signals related to adverse drug reactions of alpha-adrenoceptor antagonists and presented serious adverse events, suggesting new adverse reactions to be aware of when using alpha-adrenoceptor antagonists.

• Journal of Preventive Medicine and Public Health
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• 제42권3호
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• pp.165-170
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• 2009

Objectives : We evaluated the risk of fracture associated with hypotension-related adverse drug reaction caused by taking alpha blockers to treat benign prostatic hyperplasia (BPH). Methods : We used the Health Insurance Review and Assessment Service database from January 1st 2005 to June 30th 2006 for this study. The male patients with BPH and who had a prescription for alpha blockers following any fractures were defined as the cases. We set the 20 day long hazard period prior to the index date and the four control periods whose lengths were same with hazard period. After 1:4 matching of the hazard and control periods, conditional logistic regression was used to calculate the odds ratios for the risk of fractures as related to the alpha blocker exposure. Results : Doxazosin and tamsulosin showed the increased risk of fractures, whereas terazosin did not. After stratification using the defined daily doses, a protective effect was shown for the patients who took terazosin at the doses lower than 0.4 DDD and the hazardous effect at the doses higher than or equal to 0.4 DDD. There was no significant difference for the risk of patients taking tamsulosin at the doses higher than 1.0 DDD but there was a statistically significant increase in the risk at the doses higher than or equal to 1.0 DDD. Conclusions : Alpha blockers for BPH may increase the risk of fracture in elderly patients who have comorbidities and take the concomitant medications. Alpha blockers need to be prescribed with caution, although some have high prostate specificity.