• Journal of Pharmaceutical Investigation
• /
• v.38 no.2
• /
• pp.135-142
• /
• 2008

The present study describes the evaluation of the bioequivalence of two atorvastatin tablets, Lipitor $Tablet^{(R)}$ (Pfizer, reference drug) and Atorva $Tablet^{(R)}$ (Yuhan, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Forty-nine healthy male Korean volunteers received each medicine at the atorvastatin dose of 40 mg in a $2{\times}2$ crossover study with a two weeks washout interval. After drug administration, serial blood samples were collected at a specific time interval from 0-48 hours. The plasma atorvastatin concentrations were monitored by an high performance liquid chromatography -tandem mass spectrometer (LC-MS/MS) employing electrospray ionization technique and operating in multiple reaction monitoring (MRM) and positive ion mode. The total chromatographic run time was 4.5 min and calibration curves were linear over the concentration range of 0.1-100 ng/mL for atorvastatin. The method was validated for selectivity, sensitivity, linearity, accuracy and precision. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 48hr) was calculated by the linear log trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were complied trom 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 $C_{max}$ ratio for Atorva $Tablet^{(R)}$ / Lipitor $Tablet^{(R)}$ were ${\log}\;0.9413{\sim}{\log}\;1.0179$ and ${\log}\;0.831{\sim}{\log}\;1.0569$, respectively. These values were within the acceptable bioequivalence intervals of ${\log}\;0.8{\sim}{\log}\;1.25$. Based on these statistical considerations, it was concluded that the test drug, Atorva $Tablet^{(R)}$ was bioequivalent to the reference drug, Lipitor $Tablet^{(R)}$.

• The Korean Journal of Physiology and Pharmacology
• /
• v.5 no.1
• /
• pp.71-78
• /
• 2001

Capsaicin, a pungent ingredient of hot pepper, elicits an intense burning pain when applied cutaneously and intradermally. Activation of capsaicin-gated channel in C-type dorsal root ganglion (DRG) neurons produces nonselective cationic currents. Although electrophysiological and biochemical properties of capsaicin-activated current $(I_{CAP})$ were studied, the regulatory mechanism and intracellular signaling pathway are still unclear. In the present study, we investigated the modulations of $I_{CAP}$ by DAMGO $({\mu}-opioid\;agonist)$ and cholecystokinin octapeptide (CCK-8). In 18 out of 86 cells, the amplitude of $I_{CAP}$ was significantly increased by DAMGO and completely reversed after washout, while $I_{CAP}$ was decreased by DAMGO in 25 cells. In 43 cells, DAMGO had no effect on $I_{CAP}$. Mean action potential duration was significantly different between 'increased-by-DAMGO' group and 'decreased-by-DAMGO' group. Mean amplitudes of $I_H$ were not significantly different between both groups. CCK-8 reversibly enhanced the amplitude of $I_{CAP}$ (5/13). DAMGO also increased $I_{CAP}$ amplitude significantly in the same cells. The amplitude of $I_{CAP}$ was increased in additive manner by combined applications of DAMGO and CCK-8 in these cells. These results suggest that DAMGO and CCK-8 can either increase or decrease $I_{CAP}$ presumably depending on the subtypes of DRG cells and classified by electrophysiological properties.

• The Korean Journal of Physiology and Pharmacology
• /
• v.19 no.1
• /
• pp.65-71
• /
• 2015

Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR) and reversible airway obstruction. Methacholine (MCh) is widely used in broncho-provocation test to evaluate airway resistance. For experimental investigation, ovalbumin-induced sensitization is frequently used in rodents (Ova-asthma). However, albeit the inflammatory histology and AHR in vivo, it remains unclear whether the MCh sensitivity of airway smooth muscle isolated from Ova-asthma is persistently changed. In this study, the contractions of airways in precision-cut lung slices (PCLS) from control, Ova-asthma, and IL-13 overexpressed transgenic mice (IL-13TG) were compared by analyzing the airway lumen space (AW). The airway resistance in vivo was measured using plethysmograph. AHR and increased inflammatory cells in BAL fluid were confirmed in Ova-asthma and IL-13TG mice. In the PCLS from all three groups, MCh concentration-dependent narrowing of airway lumen (${\Delta}AW$) was observed. In contrast to the AHR in vivo, the $EC_{50}$ of MCh for ${\Delta}AW$ from Ova-asthma and IL-13TG were not different from control, indicating unchanged sensitivity to MCh. Although the AW recovery upon MCh-washout showed sluggish tendency in Ova-asthma, the change was also statistically insignificant. Membrane depolarization-induced ${\Delta}AW$ by 60 mM $K^+$ (60K-contraction) was larger in IL-13TG than control, whereas 60K-contraction of Ova-asthma was unaffected. Furthermore, serotonin-induced ${\Delta}AW$ of Ova-asthma was smaller than control and IL-13TG. Taken together, the AHR in Ova-asthma and IL-13TG are not reflected in the contractility of isolated airways from PCLS. The AHR of the model animals seems to require intrinsic agonists or inflammatory microenvironment that is washable during tissue preparation.

• Journal of Veterinary Clinics
• /
• v.19 no.3
• /
• pp.283-289
• /
• 2002

The effects of electroacupuncture (EA) at SP-6 with different durations on the minimum alveolar concentration (MAC) and on the cardiovascular system were evaluated in dogs under isoflurane anesthesia. Eight healthy male beagles were randomly assigned to four study groups (n = 5/group) with washout period of 7 days for recovery and anesthetic withdrawal between experiments. Four study groups were control, nonacupoint electrical stimulation (NA), EA for 30 minutes (SP-6) and continuous EA for 70 or 90 minutes (SP-6C). For the nonacupoint electrical stimulation group, needles were inserted into the nonacupoint at the muscle bellies of left triceps brachii and right quadriceps femoris. MAC and cardiovascular parameters were determined after EA at SP-6 acupoint and at nonacupoint. Thirty minutes of EA and continuous EA until re-determination of MAC at SP-6 acupoint lowered the MAC of isoflurane by 21.3$\pm$8.0% and 16.1$\pm$4.6%, respectively (p<0.05). The decrements in MAC values were not significantly different between two EA groups. However, electrical stimulation of nonacupoint did not induce a significant change in MAC. In SP-6 and SP-6C groups, significant changes in cardiovascular parameters were not observed. These results indicate that EA at SP-6 have an advantage in isoflurane anesthesia in terms of reducing the requirement for anesthetics and minimizing cardiovascular side effects. EA for 30 minutes at maximum might be the sufficient time to produce acupuncture analgesia.

• Archives of Pharmacal Research
• /
• v.29 no.4
• /
• pp.328-332
• /
• 2006

The bioequivalence and pharmacokinetics of alendronate sodium tablets were examined by determining the plasma concentration of alendronate. Two groups, consisting of 24 healthy volunteers, each received a 70 mg reference alendronate sodium tablet and a test tablet in a $2{\times}2$ crossover study. There was a 6-day washout period between doses. The plasma alendronate concentration was monitored for 7 h after the dose, using HPLC-Fluorescence Detector (FD). The area under the plasma concentration-time curve from time 0 to the last sampling time at 7 h $(AUC_{0-7h})$ was calculated using the linear-log trapezoidal rule. The maximum plasma drug concentration $(C_{max})$ and the time to reach $C_{max}(T_{max})$ were derived from the plasma concentration-time data. Analysis of variance was performed using logarithmically transformed $AUC_{0-7h}\;and\;C_{max}$, and untransformed $T_{max}$. For the test medication versus the reference medication, the $AUC_{0-7h}\;were\;87.63{\pm}29.27\;vs.\;102.44{\pm}69.96ng\;h\;mL^{-1}$ and the $C_{max}$ values were $34.29{\pm}13.77\;vs.\;38.47{\pm}24.39ng\;mL^{-1}$ respectively. The $90\%$ confidence intervals of the mean differences of the logarithmic transformed $AUC_{0-7h}$ and $C_{max}$ values were log 0.8234-log 1.1597 and log 0.8222-log 1.1409, respectively, satisfying the bioequivalence criteria guidelines of both the US Food and Drug Administration and the Korea Food and Drug Administration. The other pharmacokinetic parameters for the test drug versus reference drug, respectively, were: $t_{1/2},\;1.87{\pm}0.62\;vs.\;1.77{\pm}0.54\;h;\;V/F,\;2061.30{\pm}986.49\;vs.\;2576.45{\pm}1826.05\;L;\;CL/F,\;835.32{\pm}357.35\;vs.\;889.48{\pm}485.87\;L\;h^{-1}; K_{el},\;0.42{\pm}0.14\;vs.\;0.40{\pm}0.18\;h^{-1};\;Ka,\;4.46{\pm}3.63\;vs.\;3.80{\pm}3.64\;h^{-1};\;and\;T_{lag},\;0.19{\pm}0.09\;vs.\;0.18{\pm}0.06\;h$. These results indicated that two alendronate formulations(70-mg alendronate sodium) were biologically equivalent and can be prescribed interchangeably.

• Journal of The Korean Society of Integrative Medicine
• /
• v.9 no.3
• /
• pp.165-173
• /
• 2021

Purpose : Myofascial decompression is frequently mentioned as a method applied to cupping. The purpose of this study is to evaluate and compare active range of motion (AROM), muscle strength, and functional movement by applying myofascial decompression to the hamstrings. Methods : This study evaluated AROM, muscle strength, and functional movement by applying active movement myofascial decompression and static myofascial decompression to the dominant leg, respectively, in a crossover design conducted with normal adults (n=21) in their average 20s enrolled at G University in G city, Gyeongsangbuk-do. Active movement myofascial decompression was implemented for five minutes at a rate of 100 bpm to make the beats in flexion and extension respectively. Static myofascial decompression was only performed for five minutes while at rest. All of these interventions were performed at a cupping depth of two mm. After a one-week washout period, static was applied again to compare the same dependent variables. Results : Regarding AROM and muscle strength, both groups showed significant differences in the before and after results (p<.05). However, in the Functional Reach Aspect and Single Leg Hop test, the active movement myofascial decompression group showed better results. There was no statistical difference between the Active movement myofascial decompression group and Static myofascial decompression group in any dependent variable (p<.05). Conclusion : As a result of this experiment, both active movement myofascial decompression and static myofascial decompression had a positive effect on dependent variable. Therefore this study is meaningful in that it is easier and simpler to see the effect on flexibility, muscle strength, and functional movement just by implementing movement myofascial decompression.

• The Journal of Internal Korean Medicine
• /
• v.43 no.4
• /
• pp.582-595
• /
• 2022

Objectives: To investigate the effects of acupuncture at GV20 and EX-HN1 on cerebral blood flow (CBF) velocity and cerebrovascular reactivity (CVR) in the middle cerebral arteries (MCA) and anterior cerebral arteries (ACA) and to compare the effects to acupuncture at GV20. Methods: The study was a randomized, crossover trial that included 10 healthy men aged 20 to 29 years who underwent acupuncture treatment four times with a washout period of one week. The CBF velocity and CVR were measured by transcranial Doppler sonography (TCD) on both MCAs at the first and second visits, and both ACAs at the third and fourth visits. Participants were randomly assigned to one of two groups (A and B) before the first and third visits. Group A received two phases of acupuncture intervention at a single GV20 point and a combination of GV20 and EX-HN1 acupoints. Group B received the same interventions, but in the reverse order. Results: The increase in CO₂ reactivity was significantly higher for the combination acupoints of GV20 and EX-HN1 than for the GV20 single acupoint in both MCAs (Right: 136 to 178, p=0.017; Left: 127 to 191, p=0.017) and ACAs (Right: 133 to 158, p=0.013; Left: 122 to 168, p=0.025). No significant change was noted in the corrected velocity at PETCO₂ 40 mmHg, blood pressure, or heart rate. Conclusions: The findings suggest that improvement of the CBF in the MCA and ACA after GV20 acupuncture increases when acupuncture is also performed at EX-HN1. These results clinically support the combined use of EX-HN1 and GV20 to treat disorders of MCA and ACA circulation.

• Journal of the Korean Recycled Construction Resources Institute
• /
• v.10 no.4
• /
• pp.482-488
• /
• 2022

In this study, the durability of ultra rapid hardening mortar for sewage pipe was evaluated by type of mortar binder. As a result of analyzing the internal structure for each type of mortar, it was confirmed that Al₂(OH)₃ was generated in the internal structure of the CAC-based mortar, and its corrosion resistance was superior to that of other types of mortar. As a result of the compressive strength test, OPC had the tsmallest strength, followed by CAC100 > CAC100P > CAC80. This trend was similar to the previous study results. Chloride ion penetration resistance and freeze-thaw test showed similar trends. That is, CAC and C12A7 were better than OPC, and CSA was worse than OPC. This is mostly beacuse of cracks caused by expansion of CSA-based mortar. CAC100P mix showed the best chemical resistance. It is thought that this is because the alumina gel formed inside the mortar and the polymer combine to make the internal structure more dense.

• The Journal of Korean Medicine
• /
• v.43 no.2
• /
• pp.61-74
• /
• 2022

Objectives: This study aimed to explore the short-term effects of bilateral masticatory training using an intraoral device on memory and concentration, which is an advanced form of Gochi, compared to the unilateral form with gum. Methods: Thirty young healthy participants (age, 16-30 years) were screened and randomly assigned to one of two sequences in a crossover design. The participants assigned to sequence A (n=15) performed bilateral mastication using an intraoral device with a total of 300 taps, followed by unilateral mastication using gum with the same number of repetitions and frequency, separated by a 7-day washout period. A reverse order was used for sequence B. The primary and secondary outcomes were the digit span test result and the symbol digit modality test and the word list recall results, respectively, which were conducted before and after each intervention. Results: Symbol digit modality test scores increased by 12.03±8.33 with bilateral mastication, which was significantly higher than that obtained with chewing gum (5.17 points;95% confidence interval: 0.99, 9.34; p<0.05). Changes in the digit span test and word list recall scores were not significantly different between the two groups. In the digit span test forward, symbol digit modality test, and word list recall test, bilateral mastication was not inferior to unilateral mastication in improving memory and concentration. Conclusions: Bilateral masticatory exercises using an intraoral device are not inferior to unilateral mastication with gum for improving memory in healthy young individuals. Further research is needed to determine the efficacy of bilateral masticatory training on cognitive function.

• Journal of Life Science
• /
• v.33 no.8
• /
• pp.639-650
• /
• 2023

The levels of harmful components in aerosols from heated tobacco products (HTPs) have been reported to be significantly lower than in cigarette smoke. However, it remains unclear whether the use of HTPs can mitigate the cardiovascular risks associated with cigarette smoking (CS). The objective of this study was to investigate the effects of a short-term switch from CS to HTP use on cardiac autonomic regulation (CAR). Seven healthy male smokers completed an open-label, randomized, cross-over trial consisting of five days of CS, use of three different HTPs (IQOS use, IQ; lil SOLID use, LS; lil HYBRID use, LH), or non-smoking (NS). Each session was separated by a one-week washout period, and levels of exhaled carbon monoxide (CO) and carboxyhemoglobin (COHb), systolic (SBP) and diastolic blood pressure (DBP), and heart rate variability (HRV) reflecting CAR were assessed before use of the product assigned to each session and at 24, 48, 72, 96, and 120 hr after use. Levels of exhaled CO and COHb were statistically significantly reduced only during NS. There were no statistical changes in SBP and DBP within any session. However, in HRV spectral analysis, log-transformed high frequency (lnHF) increased statistically significantly in IQ, LS, and NS, respectively. Normalized HF (HFnu) was significantly increased in NS and LH, respectively. lnHF and HFnu showed significant interaction effects. The findings of this study suggest that a short-term switch to HTPs instead of CS may lead to different distribution patterns of CAR, primarily driven by enhanced cardiac vagal tone.