• Journal of Pharmaceutical Investigation
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• v.28 no.4
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• pp.283-288
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• 1998

Lovastatin, one of the potent cholesterol-lowering agents, is an inactive lactone prodrug which is metabolized to its active open acid, lovastatin acid (LVA). Bioequivalence study of two lovastatin preparations, the test drug ($Mevacor^{\circledR}$: Chungwae Pharmaceutical Co., Ltd.) and the reference drug ($Lovaload^{\circledR}$: Chong Kun Dang Pharmaceutical Co., Ltd.), was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Fourteen healthy male volunteers, $23.9{\pm}3.9$ years old and $67.6{\pm}8.0$ kg of body weight in average, were divided randomly into two groups and administered the drug orally at the dose of 160 mg as lovastatin in a $2{\times}2$ crossover study. Plasma concentrations of lovastatin acid were analysed by HPLC method for 12 hr after administration. The extent of bioavailability was obtained from the plasma concentration-time profiles of total lovastatin acid after alkaline hydrolysis of the plasma samples. By alkaline hydrolysis, trace amounts of unmetabolized lovastatin were converted to lovastatin acid. The $AUC_{0-12hr}$ was calculated by the linear trapezoidal rule method. The $C_{max}$ and $T_{max}$ were compiled directly from the plasma drug concentration-time data. Student's t-test indicated no significant differences between the formulations in these parameters. Analysis of variance (ANOVA) revealed that there were no differences in AUC, $C_{max}$, and $T_{max}$ between the formulations. The apparent differences between the formulations were far less than 20% (e.g., 7.07, 5.77 and 1.18% for AUC, $C_{max}$, and $T_{max}$, respectively). Minimum detectable differences(%) between the formulations at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 17.2, 15.1, and 15.9% for AUC, Cmax, and Tmax, respectively). The 90% confidence intervals for these parameters were also within ${\pm}20%$ (e.g.. $-5.20{\sim}19.3$, $-5.00{\sim}16.5$, and $-10.2{\sim}12.5%$ for AUC, $C_{max}$, and $T_{max}$, respectively). These results satisfied the bioequivalence criteria of KFDA guidelines, indicating that the two formulations of lovastatin were bioequivalent.

• Journal of Pharmaceutical Investigation
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• v.25 no.3
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• pp.227-237
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• 1995

Omeprazole(OMP) complexes such as inclusion complexes of OMP with $hydroxypropyl-{\beta}-cyclodextrin$(HPCD) and ${\beta}-cyclodextrin({\beta}-CD)$, OMP-cholestyramine(CHL) and OMP-ethylenediamine(OMP-ED) were prepared, respectively. The partition coefficients in Witepsol H-15 /pH 7.4 phosphate buffer solution of OMP complexes$(OMP-HPCD;\;3.69{\pm}0.26,\;OMP-{\beta}-CD;\;4.08{\pm}0.21,\;OMP-CHL;\;4.36{\pm}0.25\;and\;omeprazole\;sodium(OMP-Na);\;3.64{\pm}0.37)$ were higher than that of OMP $(2.66{\pm}0.47)$. OMP was not completely dissolved until even 3 hrs, but all the OMP complexes studied were released about 100% in 20 min. The rectal suppositories containing OMP or each above OMP complex were prepared using Witepsol H-15 base, and their dissolution and stability were examined, and pharmacokinetic study were investigated after their rectal administrations to the rabbits. While the suppository containing OMP was released only less than 60% in 150 min, $OMP-{\beta}-CD$, OMP-CHL, OMP-Na and OMP-ED suppositories were all released about 65% in 20 min. Especially, OMP-HPCD suppository released OMP about 70% in 10 min. All the additives such as sodium laurylsulfate, eglumine, arginine and PVP increased drug release from OMP-HPCD suppository to some extent. The decomposition rate constants of OMP in the suppositories were $9.117{\times}10^{-3}\;day^{-l}$ for OMP suppository, $2.121{\times}10^{-2}$ for OMP-HPCD, $1.607{\times}10^{-2}$ for $OMP-{\beta}-CD$, $9.26{\times}10^{-3}$ for OMP-Na, $6.769{\times}10^{-3}$ for OMP-CHL and $5.58{\times}10^{-3}\;day^{-l}$ for OMP-ED suppository, respectively. Additives such as arginine, eglumine and ED had some stabilizing effect for OMP-HPCD, OMP-CHL and OMP-Na suppositories, respectively. After 6 month-storage at $30^{\circ}C$, 75% RH, OMP-CHL suppository was most stable. The values of Tmax for OMP-HPCD and OMP-Na suppositories were $11.7{\pm}2.36\;and\;11.4{\pm}2.56\;min$, respectively. The values of Cmax for OMP-HPCD and OMP-CHL suppository were $2.31\;{\mu}g/ml\;(p<0.01)\;and\;1.89\;{\mu}g/ml\;p<0.01)$, respectively. The values of AUC for OMP and $OMP-{\beta}-CD$ suppository were $61.9{\pm}25.79\;and\;68.6{\pm}29.48\;{\mu}g\;{\cdot}\;min/ml$, and the corresponding values for OMP-HPCD and OMP-CHL were $106.1{\pm}43.16\;(p<0.05)\;and\;127.3{\pm}42.52\;{\mu}g\;{\cdot}\;min/ml(p<0.01)$, respectively. The above results indicate the OMP-HPCD and OMP-CHL suppositories have the excellent bioavailabilties in vivo study.

• Korean Journal of Veterinary Research
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• v.46 no.1
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• pp.7-12
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• 2006

We have studied pharmacokinetics of a new anti-human immunodeficiency virus (HIV) agent VP-0501 and its amino acid prodrug VP-0501AL which is designed to improve oral bioavailability. After oral administration at 100 mg/kg dose in rats (n = 4), VP-0501 was not detectable in plasma (<50 ng/ml), while after the administration of VP-0501AL, VP-0501 was quantitatively detected, at least for 8 hrs, with Cmax of ca. $2.5{\mu}g/ml$ and AUC of $8hr^{\ast}{\mu}g/ml$. When VP-0501 was intravenously administered at 50mg/kg, this compound appeared at a marginal level in plasma with AUC of $2hr^{\ast}{\mu}g/ml$, $t_{1/2}$ of 2 hr, $C_0$ of $0.7{\mu}g/ml$, and MRT of 3 hr. On the other hand, with intravenous VP-0501AL at the same dose, both the prodrug VP-0501AL and its metabolite VP-0501 appeared comparatively at higher level in the plasma: pharmacokinetic parameters of VP-0501AL including $Vd_{\beta}$, AUC, $t_{1/2,{\beta}}$, $C_0$, $CL_{tot}$, and MRT were ca. 2 L/kg, $70hr^{\ast}{\mu}g/ml$, 2 hr, $180{\mu}g/ml$, 0.7 L/hr/kg, and 1 hr, respectively. These results demonstrate that attachment of amino acid alanine to VP-0501 is an effective approach for improvement of its oral bioavailability. Therefore, VP-0501AL is expected to become a new highly bioavailable and potent anti-AIDS drug candidate/lead compound.

• Journal of Pharmaceutical Investigation
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• v.34 no.6
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• pp.505-511
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• 2004

A bioequivalence study of $Bestidine^{TM}$ tablets (Choong Wae Pharma. Corp., Korea) to Dong-A $Gaster^{TM}$ (Dong-A Pharmaceutical Co., Ltd., Korea) tablets was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty four healthy male Korean volunteers received each medicine at the famotidine dose of 40 mg in a $2{\times}2$ crossover study. There was a one-week wash out period between the doses. Plasma concentrations of famotidine were monitored by a high-performance liquid chromatography for over a period of 12 hours after the administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 12 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the Cmax ratio for $Bestidine^{TM}/Gaster^{TM}$ were log 0.90-log 1.06 and log 0.98-log 1.20, respectively. These values were within the acceptable bioequivalence intervals of 0.80-1.25. Thus, our study demonstrated the bioequivalence of $Bestidine^{TM}$ and $Gaster^{TM}$ with respect to the rate and extent of absorption.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.30 no.1
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• pp.63-68
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• 1985

This study was conducted to investigate the dry matter production and distribution ratio of dry matter produced for each of 5 botanical types (Virginia-Small Seed, Virginia-Large Seed, Spanish, Valencia, Shinpung) of Peanut (Arachis hypogaea L.) in Peanut culture limiting region. The total dry weight increased in order of Virginia-Large seed, Virginia- Small Seed, Shinpung, Spanish, Valencia type. The maximum Crop growth rates (Cmax) were Virginia-Small seed 18.22-23.41 g/㎡/day, Virginia-Large seed 19.61-20.03 g/㎡/day, Shinpung 16.33-19.77 g/㎡/day, Spanish 13.86-16.28 g/㎡/day, Valencia 13.97-16.25g/㎡/day, respectively. LAI showed the high value at vinyl-mulching than non-mulching. In the early filling stage, distribution ratio of dry matter produced showed the highest at the shinpung type than the other types.

• Journal of Yeungnam Medical Science
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• v.14 no.1
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• pp.123-136
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• 1997

The purpose of this study was to examine the reliability and validity of a Korean form of Childhood Attention Problem(CAP) scale. CAP were administered to 98 normal elementary school students as control group and 98 attention deficit hyperactivity disorder patients. Male students showed high scores than female students in both subscale and total scores, but not statistically significant. There were no significant difference in CAP scale between male students and female students in attention deficit hyperactivity disorder patients. In the reliability test, the test-retest reliability coefficient was highly satisfactory and that of inattention subscale was 0.83, impulsivity subscale was 0.70 and total score was 0.82. In the reliability test by internal consistency, the Cronbach $\alpha$ coefficient was highly satisfactory and that of inattention subscale was 0.91, overactivity subscale was 0.89(p<0.05). The concurrent validity between CAP scale and ADDES-BV scale was 0.85 in attention deficit hyperactivity disorder patient group and 0.73 in normal control group(p<0.05). In discriminant validity test between attention deficit hyperactivity disorder patient group and normal control group, the patient group showed higher score(p<0.05). The total discriminant capacity of the patient group in CAP was 93.4%. In this point of view, CAP scale showed high reliability and validity in applying to Korean subjects and was proved to be the good and simple screening test tool for attention deficit hyperactivity disorder research and can help many young patient to treat early.

• The Korean Journal of Pharmacology
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• v.26 no.2
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• pp.219-226
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• 1990

Enalapril maleate tablets of two different producers were tested for bioequivalence. Enalapril is rapidly metabolized to an active metabolite, enalaprilat which inhibits angiotensin-converting enzyme (ACE). The pharmacokinetics of enalapril maleate and the time course of inhibition of plasma ACE activity after administration of the drugs were studied. Two single doses of 10mg each of enalapril maleate were administered orally to twelve male volunteers in a balanced, randomized, two-way crossover investigation. Plasma enalaprilat concentrations were determined over a 23-hour after the dose by enzyme inhibition assay and enalapril by the same method following in vitro hydrolysis. Urinary recoveries of enalapril and enalaprilat were determined for the calculation of renal clearance. Plasma ACE activity was determined by an enzyme assay. Peak plasma levels of enalapril were observed about 1 hour after the doses, and practically all enalapril had disappeared from plasma within 6 hour. Peak enalapril concentrations of both formulations were almost identical ($Vasotec^{\circledR}$, 61.38 ng/ml; $Beartec^{\circledR}$, 64.27 ng/ml). The values of the pharmacokinetic parameters of enalaprilat computed for $Vasotec^{\circledR}$ and $Beartec^{\circledR}$ tablets are presented in that order; area under the curve=330.63:320.96 $ng{\cdot}hr/ml$; peak concentration=38.63:39.43 ng/ml; time to peak=3.83:4.08 hour; elimination half-life=3.95:3.92 hours. No statistically significant difference was detected when area under the curve and all other parameters were compared. Using criteria of 95% confidence interval for the comparison of these parameters, only the upper limits of area under the curve and time to peak of enalapril were over 120%. All the parameters of enalaprilat were acceptable. Percent inhibition of plasma ACE to plasma enalaprilat concentration showed the sigmoid concentration-inhibition relationship. Time courses of plasma ACE inhibition after the administration of both formulations were quite similar. The formulations were found to be equivalent when compared on the premise that no significant difference was detected when pharmacokientic parameters and inhibition of ACE activity were compared, based on the confidence limits analysis.

• Journal of Yeungnam Medical Science
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• v.14 no.2
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• pp.415-429
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• 1997

The purpose of this study was to examine the reliability and validity of attention deficit disorder evaluation scale-school version(ADDES-SV). Between October 1996 and November 1996, ADDES-SV was administered to 263 elementary school students in the second grade and between Jun 1996 and October 1996, 28 attention deficit hyperactivity disorder patients. In the reliability test, the test-retest reliability coefficient was significantly high and that of inattention was 0.88, that of impulsivity was 0.80, that of hyperactivity was 0.83 and total score was 0.83. In the reliability test by internal consistancy, the Cronbach $\alpha$ coefficient was significantly high and that of inattention was 0.98, that of impulsivity was 0.87, that of hyperactivity was 0.87(p<0.05). The half-sprit reliability coefficient by first-second half method showed high correlation and that of inattention was part 1: 0.96, part 2: 0.96 impulsivity was part 1: 0.95, part 2: 0.93, hyperactivity was part 1: 0.92, part 2: 0.94(p<0.05). Inter-rater reliability by pearson correlation coefficient was significantly high and that of inattention was 0.92, that of impulsivity was 0.87, that of hyperactivity was 0.89 and total score was 0.89. The concurrent validity between ADDES-SV and CAP scale was 0.85 in attention deficit hyperactivity disorder patient group and 0.79 in normal control group(p<0.05). In discriminant validity test between attention deficit hyperactivity disorder patient group and normal control group, the patient group showed higher score(p<0.05). The total discriminant capacity of the patient group in ADDES-SV was 94.6%. In this point of view, ADDES-SV scale showed high reliability and validity in applying to Korean subjects and was proved to be the useful screening test tool for attention deficit hyperactivity disorder research.

• Journal of Veterinary Clinics
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• v.18 no.3
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• pp.195-200
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• 2001

Metabolism and phamacokinetics of albendazole have been studied in Korean native cattle after oral administration of 5 mg/kg of albendazole. As ABZ is known to be rapidly biotransformed to many metabolites in most animal species, it is very imperative to establish the analytical conditions for its metabolites. LC/MS methods for ABZSO and ABZS $O_2$met every requirement enough to study the metabolism of pharmacokinetics of albendazole in Korean native cattle. The parent drug (ABZ) was only measured at first two time points of 0.5 h and 1h, whereas two metabolites were consistently formed between 0.5 h to 48-72 h post-treatment. Formation kinetics for ABZSO and ABZS $O_2$were similar. Time to peak concentration (Tmax) of ABZ-SO appeared at 12h post-treatment of ABZ, faster than that of ABZS $O_2$at 24h. Cmax of ABZS $O_2$(1.05$\pm$0.05 ug/ml) was 1.09 times higher than that of ABZSO (0.96$\pm$0.15). Elimination half-life of ABZS $O_2$(4.2 h) was much shorter than ABZS $O_2$(7.0h) (p<0.005). ABZSO was detected until 48h post-administration but ABZS $O_2$was measurable even at 72h post-dosing. AU $C_{0longrightarrow{\infty}}$ of ABZSO was smaller than that of ABZS $O_2$. Regimen of ABZ is advised to take into consideration is metabolite profiles, especially that of ABZSO, an active metabolite.

• Journal of Bio-Environment Control
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• v.30 no.4
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• pp.448-454
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• 2021

This study was conducted to the effect of low air temperature and light intensity conditions on yield and quality of tomato at the early stage of growth in Korea. Inplastic greenhouses, low temperature and low temperature with shade treatments were performed from 17 to 42 days after plant. Tomato growing degree days were decreased 5.5% due to cold treatment during the treatment period. Light intensity decreased 74.7% of growing degree days due to shade. After commencing treatments, the plant growth decreased by low temperature and low radiation except for height. Analysis of the yield showed that the first harvest date was the same, but the yield of the control was 3.3 times higher than low temperature with shade treatment. The cumulative yields at 87 days after transplanting were 1734, 1131, and 854 g per plant for control, low temperature, and low temperature with shade, respectively. The sugar and acidity of tomatoes did not differ between treatment and harvesting season. To investigate the photosynthetic characteristics according to the treatment, the carbon dioxide reaction curve was analyzed using the biochemical model of the photosynthetic rate. The results showed that the maximum photosynthetic rate, J (electric transportation rate), TPU (triose phosphate utilization), and R_d (dark respiration rate) did not show any difference with temperature, but were reduced by shading. Vcmax (maximum carboxylation rate) was decreased depending on the low temperature and the shade. Results indicated that low temperature and light intensity at the early growth stage can be inhibited the growth in the early stage but this phenomenon might be recovered afterward. The yield was reduced by low temperature and low intensity and there was no difference in quality.