• YAKHAK HOEJI
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• v.58 no.1
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• pp.40-46
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• 2014

Drugs with a narrow therapeutic index (NTI) require very precise dosing. Warfarin and digoxin are the examples of NTI-drugs and dosing of them varies widely for different patients. However, in South Korea, only two strengths of warfarin and one of digoxin are commercially available. This is a big barrier for the precise dispensing and has potential safety risks to patients, particularly to elderly patients. To find a potential solution to the problem, an analysis of the prescribed doses and dispensing patterns of those drugs was performed. Data were collected by computer-facilitated prescription review in a university hospital. The period screened was from May 1st, 2012 to April 30th, 2013. All the prescriptions with either warfarin or digoxin tablets were selected for this study and dispensing patterns were analyzed according to the prescribed doses. A total of 17,017 warfarin prescriptions were analyzed; 8,148 for inpatient prescriptions, 8,869 for outpatient prescriptions, respectively. Of the 23 kinds of prescribed doses, 2 mg (19.9%) was most frequent, followed by 3 mg (13.2%) and 2.5 mg (11.7%). By analyzing the dispensing patterns, 60.3% (10,253) of the prescriptions required pill splitting and 72.0% of them were for the patients 65 years old and over. On the other hand, 4,350 digoxin prescriptions were included in this study. Of the 6 kinds of prescribed doses, 0.125 mg (71.2%) was most frequent, followed by 0.0625 mg (20.2%). Among the prescriptions for digoxin, 92.0% (3,998) should be split and 65.7% of them were for the patients aged 65 years and over. Despite limitations of strengths, various doses of warfarin and digoxin were prescribed. Furthermore, more than half of the prescriptions that required pill splitting were for elderly patients. The results from this study suggest that different strengths of warfarin and digoxin should be provided for accuracy of dispensing and safety for patients receiving them.

• Journal of Oral Medicine and Pain
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• v.40 no.1
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• pp.10-16
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• 2015

Purpose: Pilocarpine has the effects on improvement of salivary flow and subjective symptoms for xerostomic patients. Because of unwanted side effects following its systemic administration, topical pilocarpine has been paid attention as an alternative. This study aimed to investigate effects of pilocarpine solution as mouthwash on salivary flow and adverse effects compared to systemic administration of 5 mg pilocarpine tablet in healthy subjects. Methods: The study was a double blind, placebo-controlled, crossover clinical trial. Five milligrams pilocarpine tablets, 4 mL of 2% pilocarpine solution and placebo solution were given to 12 healthy volunteers (6 males and 6 females) in a predetermined order with wash-out period of at least two days and unstimulated whole saliva was collected before and after administration of each drug. Blood pressure and pulse rate was also measured and subjective effect and potential side effects were evaluated by a self-administrated questionnaire. Results: Systemic (5 mg tablet) and topical (2% solution) use of pilocarpine significantly increased salivary flow rate in healthy subjects compared to placebo (p<0.001). In both the pilocarpine solution and tablet groups, salivary flow rates at 120 minutes after administration remained increased. Subjective effect on salivation was the largest in the pilocarpine tablet group, followed by the pilocarpine solution group (p<0.05). There was no significant difference in blood pressure and pulse rate after administration of all three drugs. Fewer side effects reported in the pilocarpine solution group than in the tablet group. Conclusions: Two percents pilocarpine solution as mouthwash increases salivary flow rate, definitely superior to placebo solution and comparable to pilocarpine tablet, with fewer side effects in healthy subjects. It indicates a possibility of pilocarpine solution as a useful alternative of pilocarpine tablets for the xerostomic patients with systemic diseases.

• Archives of Pharmacal Research
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• v.28 no.4
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• pp.488-492
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• 2005

The purpose of this study is to investigate the bioequivalence of two haloperidol 5 mg tablets, Myung In haloperidol (Myung In Pharm. Co., Ltd., test drug) and $Peridol^{R}$(Whanin Pharm. Co., Ltd., reference drug), and also to estimate the pharmacokinetic parameters of haloperidol in Korean volunteers. The bioavailability and pharmacokinetics of haloperidol tablets were examined on 24 healthy volunteers who received a single oral dose of each preparation in the fasting state in a randomized balanced 2 way crossover design. After an oral dosing, blood samples were collected for a period of 60 h. Plasma concentrations of haloperidol were determined using a liquid chromatographic electrospray mass spectrometric (LC-MS) method. The pharmacokinetic parameters were calculated with noncompartmental pharmacokinetic analysis. The geometric means of $AUC_{0-60h} and C_{max}$ between test and reference formulations were $17.21\pm8.26 ng\cdot/mL vs 17.31\pm13.24 ng\cdot/mL and 0.87\pm0.74 ng/mL vs 0.85\pm0.62 ng/mL$. respectively. The $90\%$ confidence intervals of mean difference of logarithmic transformed $AUC_{0-60h} and C_{max} were log0.9677{\sim}log1.1201 and log0.8208{\sim}log1.1981$, respectively. It shows that the bioavailability of test drug is equivalent with that of reference drug. The geometric means of other pharmacokinetic parameters ($AUC_{inf}. t_{1/2}, V_{d}/F, and CL/F$) between test drug and reference drug were $21.75\pm8.50 ng{\cdot}h/mL vs 21.77\pm15.63 ng{\cdot}h/mL, 29.87\pm8.25 h vs 29.60\pm7.56 h, 11.51\pm5.45 L vs 12.90\pm6.12 L and 0.26\pm0.09 L/h vs 0.31\pm0.17 L/h$, respectively. These observations indicate that the two formulation for haloperidol was bioequivalent and, thus, may be clinically interchangeable.

• KSBB Journal
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• v.25 no.5
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• pp.449-452
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• 2010

L-Thyroxine possessing a chiral center, the naturally occurring thyroid hormone has been used for the treatment of thyroid dysfunctions and marketed as levothyroxine (L-thyroxine) sodium salt. In this study, after extraction of levothyroxine tablet as a pre-treatment process, direct enantiomer separation of thyroxine on crown ether derived chiral columns for determination of optical purity was performed using reversed mobile phase with acid additive. The chromatographic method developed in this study was applied in the determination of optical purity of several current domestic and foreign commercialized levothyroxine tablets. Optical purity values of these commercialized L-thyroxine sodium tablets except one were higher than 99 percents.

• Journal of Pharmaceutical Investigation
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• v.29 no.3
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• pp.235-240
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• 1999

Bioequivalence of two clarithromycin tablets, the $Klaricid^{TM}$ (Ciba-Geigy Korea Ltd., Seoul, Korea) and the LG clarithromycin (LG Chemical Co., Ltd., Seoul, Korea), was evaluated according to the Korean Guidelines for Bioequivalence Test (KGBT 1998). Sixteen normal male volunteers $(20{\sim}26\;years\;old)$ were randomly divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 250 mg of clarithromycin was orally administered, blood sample was taken at predetennined time intervals, and the concentrations of clarithromycin in serum were detennined using HPLC method with electrochemical detector. The pharmacokinetic parameters $(AUC_t,\;C_{max}\;and\; T_{max})$ were calculated and ANOVA was utilized for the statistical analysis of parameters. The results showed that the differences in $AUC_t$, $C_{max}$, and $T_{max}$ between two tablets based on $Klaricid^{TM}$ tablet were 4.06%,2.67% and -9.70%, respectively. The powers $(1-{\beta})$ for $AUC_t$, $C_{max}$ and $T_{max}$ were 83.53%, 92.34% and 96.64%, respectively. Detectable differences $({\Delta})$ and 90 % confidence intervals $(a=0.05) $were all less than ${\pm}20%$. All the parameters above met the criteria of KGBT 1998, indicating that LG clarithromycin tablet is bioequivalent to $Klaricid^{TM}$ tablet.

• Journal of Pharmaceutical Investigation
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• v.37 no.6
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• pp.355-358
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• 2007

To develop a sustained-release tablet which had the similar dissolution to commercial ibudilast-loaded sustained-release capsule, the tablets were prepared using hydroxypropylmethylcellulose phthalate (HPMCP), ethylcellulose (EC) and hydroxypropylcellulose (HPC), and dissolution test were carried out with paddle method in KP. The tablet prepared only with HPMCP and EC showed sno similar dissolution pattern to the commercial product. As the ratio of HPMCP/HPC in tablet decreased, the dissolution rate of drug decreased in pH 1.2 but increased in pH 6.8. Furthermore, an ibudilast-loaded sustained-release tablet composed of [ibudilast/EC/HPMCP/HPC (10/10/170/10 mg/tab)] gave similar dissolution to commercial product in pH 1.2 for 3 h and in pH 6.8 for 10 h. Thus, it could be a potential candidate for the substitute of commercial capsule.

• Applied Biological Chemistry
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• v.40 no.5
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• pp.409-415
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• 1997

In order to find out the relationship between contained water and coloring rate of thiamine monosalts in preparations, three kinds of thiamine monorhodanate, -monoiodide, -monobromide were manufactured and investigated as powders, granules and compressed tablets, respectively. Apparent coloring rate constants and solubility in accordance with temperature changes were measured. Nature of contained water and coloration of thiamine monosalts in preparations was examined in detail. It was thereby found that if water attached in a free state, coloration occured whose degree was approximately proportional to the quantity of such water, and a linear relation was found to hold between the logarithm of the apparent coloring rate constants and the reciprocal of the absolute temperature in granules and compressed tablets.

• Biomolecules & Therapeutics
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• v.7 no.1
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• pp.59-65
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• 1999

A bioequivalence study of the Dong Wha Cisapril tablets(Dong Wha Pharm. Ind. Co., Ltd.) to the Prepulsid tablets(Janssen Korea Ltd.), formulations of cisapride, was conducted. Twenty four healthy Korean male subjects received each formulation at the dose of 5 mg as cisapride in a 2$\times$2 crossover study. There was a 1-week washout period between the doses. Plasma concentrations of cisapride were monitored by an LC/MS method for over a period of 36 h after each administration. AUC(area under the plasma concentration- time curve from time zero to infinity) was calculated by the linear trapezoidal and extrapolation method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed that there are no differences in AUC, $C_{max}$ and $T_{max}$ between the formulations. The apparent differences between the formulations in these parameters were all far less than 20% (i.e., 6.8, -6.6 and 1.8% for AUC, $C_{max}$ and $T_{max}$, respectively). Minimum detectable differences(%) at $\alpha$=0.05 and 1-$\beta$=0.8 were all less than 20% in these parameters between the formulations (i.e., 16.5, 11.4 and 16.4% for AUC, $C_{max}$ and $T_{max}$, respectively). The 90% confidence intervals for these parameters were also within 20% (i.e., -2.9~ 16.4, -13.2~0.1 and -7.8~ 11.4% for AUC, $C_{max}$ and $T_{max}$, respectively). These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 98-51). Therefore, these results indicate that the two formulations of cisapride are bioequivalent and, thus, may be prescribed interchangeably.hangeably.y.hangeably.

• Korean Journal of Clinical Pharmacy
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• v.10 no.2
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• pp.62-67
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• 2000

Terbinafine has a primary fungicidal action mediated by squalene epoxidase inhibition. Treated fungi accumulate squalene while becoming deficient in ergosterol, an essential component of fungal cell membranes. Bioequivalence of two terbinafine tablets, $Lamisil^{TM}$ (Novartis Korea Ltd., Seoul, Korea) and $Mycosil^{TM}$ (Daewon Pharmaceutical Co., Ltd., Seoul, Korea), was evaluated according to the guidelines of Korea Food and Drug Administration (KFDA). Sixteen normal male volunteers ($20\sim29$ years old) were randomly divided into two groups and a randomized $2\times2$ cross-over study was employed. After oral administration of $Mycosil^{TM}\;or\;Lamisil^{TM}$ (125 mg terbinafine), blood samples were taken at predetermined time intervals and the serum terbinafine concentrations were determined using an HPLC method with UV/VIS detector. The pharmacokinetic parameters $(AUC_t,\;C_{max}\;and\;T_{max})$ were calculated and ANOVA was utilized for the statistical analysis. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two tablets based on the $Lamisil^{TM}$ tablet were $-2.24\%,\;-7.68\%\;and\;2.92\%$, respectively. The powers %(1-\beta)\;for\;AVC_t,\;C_{max}\;and\;T_{max}\;were\;87.11\%,\;95.36\%\;and\;99.99\%$, respectively. Minimum detectable differences $(\Delta)\;and\;90\%$ confidence intervals were all less than $\pm20\%$. All these parameters met the criteria of KFDA for bioequivalence, indicating that $Mycosil^{TM}$ tablet is bioequivalent to $Lamisil^{TM}$ tablet.

• Journal of Ginseng Research
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• v.20 no.2
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• pp.125-132
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• 1996

To investigate the effect of Korean red ginseng (KRG) on male sexual function and serum lipid level, the results of KRG treatments were compared to placebo group. A total of 35 patients with psychogenic impotence were assigned to medication group with KRG (n=28) and placebo (n=7). KRG and placebo were given to each group for 2 months. Changes in symptoms such as frequency of coitus, morning erection, penile rigidity and tumescence were significantly higher in the group receiving KRG than placebo group. The overall therapeutic efficacies on erectile function were 67% for KRG group and 28% for placebo group (p <0.05). In the group treated with 9 tablets of KRG, there was tendency of better efficacy as compared to the group treated with 6 tablets of KRG. The level of serum high density lipid- cholesterol (HDL-cholesterol) was significantly elevated (p < 0.05) while the other serum lipid such as total cholesterol, tiglyceride and low density lipid-cholesterol (LDL-cholesterol) , were not changed after administration of KRG. This effect was observed significantly in the group in which KRG exerted its effect on sexual function(p < 0.05). From the above results, the administration of Korean red ginseng has shown to have superior of facts as compared to the placebo. The tendency of good effect was increased when a large amount of KRG was administered. The mechanism of KRG in improving sexual function would be the result of elevating the level of geum HDL-cholesterol in impotent patients. The effect of KRG was produced when the level of cholesterol was high before starting KRG medication. Therefore, the effect of KRG could be observed more intensively when the patients have high serum cholesterol level.