• Anxiety and mood
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• v.2 no.1
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• pp.39-44
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• 2006

Objective : Chronic posttraumatic stress disorder (PTSD) is defined by the coexistence of symptoms (reexperiencing, avoidance and hyperarousal), persisting for more than months or years that causes significant impairment in social occupational functioning. This study was conducted to evaluate the effects of terazosin on posttraumatic nightmares which is one of chronic PTSD symptoms. Methods : Twenty patients with chronic PTSD and severe trauma-related nightmares were treated with terazosin (3-7 mg/day) for 8 weeks. Recurrent distressing dreams item of the Clinician administered PTSD Scale (CAPS), Total CAPS score, Clinical Global Impressions-Severity Scale (CGI-S) and Clinical Global Impressions-Change Scale (CGI-C) were performed at baseline, 4-week and 8-week. Mississippi Scale for Combat-Related PTSD and Combat Exposure Scale (CES) were used to evaluate PTSD symptom pattern and degree of exposure. Results : Significant decrease in recurrent distressing dreams item, reexperiencing, avoidance and hyperarousal symptom score and total CAPS score were at 4-week and 8-week treatment compared to baseline (recurrent distressing dreams item : $2.70{\pm}1.88$ and $1.25{\pm}1.49$ ; reexperiencing, avoidance and hyperarousal symptom score : $2.30{\pm}2.49$, $1.20{\pm}1.05$, $3.10{\pm}1.68$ and $4.00{\pm}3.59$, $1.55{\pm}1.50$, $5.60{\pm}3.23$ ; total CAPS score : $8.20{\pm}6.26$ and $5.40{\pm}5.89$). There were significant correlation between dosage of terazosin and improvement of PTSD symptoms. Adverse effects such as fatigue and orthostatic hypotension were showed, which were mild and self-limited. Conclusion : These results suggest that terazosin may improve severe trauma-related nightmares and overall PTSD symptoms. Randomized controlled study with more subjects would be necessary in the future.

• Journal of Pharmaceutical Investigation
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• v.29 no.1
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• pp.61-66
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• 1999

Bioequivalence of two terazosin tablets, the $Hytrine^{TM}$ (Il-Yang Pharmaceutical Co., Ltd.) and the $Hytrine^{TM}$ (Daewon Pharmaceutical Co., Ltd.), was evaluated according to the guideline of KFDA. Sixteen normal male volunteers $(21{\sim}30\;years\;old)$ were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 2 mg of terazosin was orally administered, blood was taken at predetermined time intervals and the concentration of terazosin in serum was determined with a HPLC method using spectrofluorometric detector. The pharmacokinetic parameters $(AUC_t,\;C_{max}\;and\;T_{max})$ were calculated and ANOVA 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 6.02%,3.44% and -3.67%, respectively. The powers $(1-{\beta})$ for $AUC_t$, $C_{max}$ and $T_{max}$ were 98.05%, 98.34% and 29.81 %, respectively. Detectable differences $({\Delta})$ and confidence intervals were all less than ${\pm}20%$ except $T_{max}$. $AUC_t$ and $C_{max}$ met the criteria of KFDA for bioequivalence, indicating that $Terasin^{TM}$ tablet is bioequivalent to $Hytrine^{TM}$ tablet.

• Journal of Pharmaceutical Investigation
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• v.32 no.2
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• pp.119-125
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• 2002

A rapid, selective and reproducible high-performance liquid chromatographic method has been developed for the determination of terazocin in human plasma. Terazocin plus the internal standard, prazocin hydrochloride, were extracted from alkalified plasma with tert-butylmethyl ether, back-extracted into 0.05% phosphoric acid. Fifty ${\mu}l-portions$ of extract were injected onto a octadecylsilane column and eluted with a mixture of acetonitrile, water and triethylamine (30 : 70 : 0.1 v/v, adjusted to pH 5.0 with dilute phosphoric acid) at a flow rate of 1.0 ml/min. The fluorescence intensity of column eluents was monitored at excitation wavelength of 250 nm and emission wavelength of 370 nm. No interference peaks were observed. The practical limit of quantitation was 5 ng/ml for terazocin. The average intraday and interday coefficients of variation were 4.15 and 3.54%, respectively. Also intraday and interday precisions over the range $5{\sim}60\;ng/ml$ were $0.49{\sim}2.92\;and\;0.38{\sim}5.12%$, respectively. The bioequivalence of two terazosin tablets, the $Hytrine^{\circledR}$ (Il Yang Pharmaceutical Co., Ltd.) and the $Teratonin^{\circledR}$ (Sam-A Pharmaceutical Co., Ltd.), was evaluated according to the guideline of Korea Food and Drug Administration (KFDA). Sixteen healthy male volunteers $(24.6{\pm}2.0\;years\;old)$ were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 2 mg of terazosin was orally administered, blood was taken at predetermined time intervals and the concentration of terazosin in plasma was determined with a HPLC method using spectrofluorometric detector. AUC was calculated by the linear trapezoidal method. $C_{max}\;and\;T_{max}$ were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between the two preparations were 0.21 %, 5.53% and 8.82%, respectively. The powers $(1-{\beta})\;for\;AUC_t,\;C_{max}\;and\;T_{max}$ were >99%, 97.49%, and 33.26%, respectively. Minimum detectable differences $({\Delta},\;%)\;at\;{\alpha}=0.1\;and\;1-{\beta}=0.8$ and the 90% confidence intervals were all less than ${\pm}20%$ except for $T_{max}.\;AUC_t\;and\;C_{max}$ met the criteria of KDFA for bioequivalence, indicating that $Teratonin^{circledR}$ tablets are bioequivalent to $Hytrine^{circledR}$ tablets.

• Biomolecules & Therapeutics
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• v.13 no.2
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• pp.90-94
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• 2005

Prazosin hydrochloride is an antihypertensive drug with selective ${\alpha}_1$-adrenoreceptor blocking effects. A simple high performance liquid chromatographic method has been developed and validated for the quantitative determination of prazosin in human plasma. A reversed-phase C18 column was used for the separation of prazosin and terazosin (internal standard) with a mobile phase composed of water, acetonitrile and triethylamine(75:25:0.1, V/V;pH5.0) at a flow rate of 1.5 ml/min. the fluorescence detector was set at excitation and emissionwavelengths of 250 and 370 nm, respectively. Intra-and inter-day precision and accuracy were acceptable for all quality control samples including the lower limit of quantification of 0.5 ng/ml. Good recovery (>80%) was seen in plasma. Prazosin was stable in human plasma under various storage conditions. This method was used successfully for a pharmacokinetic study in plasma after oral administration of a single 2-mg dose as prazosin base to 16 healthy volunteers. The maximum plasma concentration of prazosin was 23.1 ${\pm}$ 16.5 ng/ml at 2.1 h, and the mean area under the curve and elimination half-life were calculated to be 108.4 ${\pm}$ 74.2 ng ${\cdot}$hr/ml and 2.5 ${\pm}$ 0.6 h, respectively.

• Biomolecules & Therapeutics
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• v.14 no.1
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• pp.40-44
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• 2006

Mirtazapine is an antidepressant agent with dual action on both the noradrenergic and serotonergic neurotransmitter systems. A simple high performance liquid chromatographic method has been developed and validated for the quantitative determination of mirtazapine in human plasma. A reversed-phase Cl8 column was used for the determination of mirtazapine with a mobile phase composed of 0.01M ammonium acetate solution (pH 4.2) and acetonitrile (75:25, v/v%) at a flow rate of 1.2 mL/min. Terazosin hydrochloride was used as an internal standard. The fluorescence detector was set at excitation and emission wavelengths of 290 and 350 nm, respectively. Intra- and inter-day precision and accuracy were acceptable for all quality control samples including the lower limit of quantification of 3 ng/mL. Mirtazapine was stable in human plasma under various storage conditions. This method was used successfully for a pharmacokinetic study using plasma samples after oral administration of a single 30 mg dose as mirtazapine base to 8 healthy volunteers. The maximum plasma concentration of mirtazapine was $64.1{\pm}28.0ng/mL$ at 1.8 h, and the area under the curve and elimination half-life were calculated to be $674.1{\pm}218.5ng\;h/mL\;and\;23.4{\pm}3.8h$, respectively.

• Proceedings of the Korean Society of Veterinary Clinics Conference
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• 2008.05a
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• pp.77-77
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• 2008

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.105-105
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• 2003

A rapid and reproducible high performance liquid chromatographic assay of prazosin in human plasma was developed. After addition of internal standard (IS, terazosin hydrochloride) and alkalization of the plasma, the drug and IS were extracted into t-butylmethylether. The organic phase was back-extracted into 0.05% phosphoric acid and 50 ${\mu}\ell$ of the acid solution was injected into a reverse-phase C18 column with a mobile phase consisting of water : acetonitrile : triethylamine = 75 : 25 : 0.1 (pH 5.0). The samples were detected utilizing a fluorescence detector. A

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.245.2-245.2
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• 2003

A rapid and reproducible high performance liquid chromatographic assay of prazosin in human plasma was developed. After addition of internal standard (IS, terazosin hydrochloride) and alkalization of the plasma, the drug and IS were extracted into t-butylmethylether. The organic phase was back-extracted with 0.05% phosphoric acid and 50 ${\mu}$l of the acid solution was injected into a reverse-phase C18 column with a mobile phase consisting of water: acetonitrile: triethylamine = 75 : 25 : 0.1 (pH 5.0). (omitted)

• Journal of Preventive Medicine and Public Health
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• v.42 no.3
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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.

• The Korean Journal of Pain
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• v.9 no.2
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• pp.318-325
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• 1996

Background: Sympathectomy relieves pain in sympathectically maintained pain, and subcutaneous injection of norepinephrine(NE) can rekindle mechanical allodynia. However, the mechanism of rekindling is not clear. The purpose of this study is to investigate which subtype of $\alpha$-adrenoceptor is involved in NE-induced rekindling of mechanical allodynia in sympathectomized neuropathic rats. Methods: Neuropathic injury was produced by tightly ligating the left L5 and L6 spinal nerves of 36 male Sprague-Dawley rats and bilateral lumbar sympathectomy was done at two weeks postoperatively. Starting at 7 days after sympathectomy, rekindling of mechanical allodynia was induced by NE and clonidine injected into the left paw, which was reversed by pretreatment of phentolamine and idazoxan. Mechanical allocynia was quantified by measuring the frequency of foot lifts to two von Frey filaments applied to the paw. Results: All tested rats displayed well-developed signs of mechanical allodynia at the left paw that were abolished by a bilateral lumbar sympathectomy. Subcutaneous (s.c.) injection of NE (0.05 ${\mu}g$) into the affected paw of sympathectomized neuropathic rats rekindled previous mechanical allodynia. These effects could be mimicked by an ${\alpha}_2$-receptor agonist clonidine, but not by an ${\alpha}_1$-receptor agonist phenylephrine. The NE-induced rekindling of mechanical allodynia was significantly reduced by prior s.c. injection of a mixed $\alpha$-receptor antagonist phentolamine (20${\mu}g$) and ${\alpha}_2$-receptor antagonist idazoxan(20${\mu}g$), but not by a ${\alpha}_1$-receptor antagonist terazosin (20${\mu}g$). The pretreatment of idazoxan produced dose-related inhibition of NE-induced rekindling of mechanical allodynia. The rekindling induced by ${\alpha}_2$-receptor agonist clonidine (5${\mu}g$) was also reversed by prior s.c. injection of ${\alpha}_2$-receptor antagonist idazoxan (20${\mu}g$). Conclusion: Subcutaneous injection of NE into the paw of sympathectomized neuropathic rats rekindles mechanical allodynia, which is reversed by an ${\alpha}_2$-, but not by an ${\alpha}_1$-receptor antagonist. Therefore, rekindling of mechanical allodynia in sympathectomized neuropathic rats is mediated by ${\alpha}_2$-adrenoceptor.