• Korean Journal of Clinical Pharmacy
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• v.26 no.4
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• pp.312-317
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• 2016

Objective: Midazolam is mainly metabolized by cytochrome P450 (CYP) 3A. Inhibition or induction of CYP3A can affect the pharmacological activity of midazolam. The aims of this study were to develop a population pharmacokinetic (PK) model and evaluate the effect of CYP3A-mediated interactions among ketoconazole, rifampicin, and midazolam. Methods: Three-treatment, three-period, crossover study was conducted in 24 healthy male subjects. Each subject received 1 mg midazolam (control), 1 mg midazolam after pretreatment with 400 mg ketoconazole once daily for 4 days (CYP3A inhibition phase), and 2.5 mg midazolam after pretreatment with 600 mg rifampicin once daily for 10 days (CYP3A induction phase). The population PK analysis was performed using a nonlinear mixed effect model ($NONMEM^{(R)}$ 7.2) based on plasma midazolam concentrations. The PK model was developed, and the first-order conditional estimation with interaction was applied for the model run. A three-compartment model with first-order elimination described the PK. The influence of ketoconazole and rifampicin, CYP3A5 genotype, and demographic characteristics on PK parameters was examined. Goodness-of-fit (GOF) diagnostics and visual predictive checks, as well as bootstrap were used to evaluate the adequacy of the model fit and predictions. Results: Twenty-four subjects contributed to 900 midazolam concentrations. The final parameter estimates (% relative standard error, RSE) were as follows; clearance (CL), 31.8 L/h (6.0%); inter-compartmental clearance (Q) 2, 36.4 L/h (9.7%); Q3, 7.37 L/h (12.0%), volume of distribution (V) 1, 70.7 L (3.6%), V2, 32.9 L (8.8%); and V3, 44.4 L (6.7%). The midazolam CL decreased and increased to 32.5 and 199.9% in the inhibition and induction phases, respectively, compared to that in control phase. Conclusion: A PK model for midazolam co-treatment with ketoconazole and rifampicin was developed using data of healthy volunteers, and the subject's CYP3A status influenced the midazolam PK parameters. Therefore, a population PK model with enzyme-mediated drug interactions may be useful for quantitatively predicting PK alterations.

• Tuberculosis and Respiratory Diseases
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• v.76 no.6
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• pp.269-275
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• 2014

Background: The six-minute walk test has been widely used in people with chronic cardiopulmonary disorders as an outcome assessment with regards to therapeutic or prognostic determinants. This study was undertaken to determine the six-minute walk distance (6MWD) in a sample of healthy Koreans and to create a reference equation. We also compared the 6MWD of our cohort with previously published equations. Methods: Two hundred fifty-nine healthy subjects (95 males) aged 22-59 years performed two walking tests using a standardized protocol. 6MWD was defined as the greatest distance achieved from the two tests. The effect of anthropometrics on the 6MWD was also investigated. Results: The average 6MWD was $598.5{\pm}57.92m$, with significantly longer distances by males ($628.9{\pm}59.51m$) than females ($580.9{\pm}47.80m$) (p<0.001). Age, height, weight, and body mass index were significantly correlated with 6MWD in univariate analysis. Stepwise multiple regression showed height to be single independent predictor of 6MWD ($r^2$=0.205, p<0.001). The reference equations derived in Caucasian and North African populations tend to overestimate the distance walked by Korean subjects, while Asian equations underestimate it. Conclusion: The average 6MWD in these Korean populations was 600 m. The regression equation revealed that individual's height was the most significant predictor of distance, explaining 20.5% of the distance variance.

• The Journal of Korean Medicine
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• v.28 no.2 s.70
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• pp.80-92
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• 2007

Objectives : Functional dyspepsia (FD) is one of the most common gastrointestinal diseases. Nevertheless, there are many unknown mechanisms of autonomic functioning in FD patients. This study was designed to investigate the relationship between FD and biosignals from heart rate variability (HRV) and Yangdorak diagnosis. Methods : 32 patients (22 female, 10 male; mean age 40) and 32 healthy volunteers (21 female, 11 malemean; age 38) participated in this study. First gastrointestinal symptoms rating scale (GSRS) was assessed by questionnaires in both groups to evaluate the types of gastrointestinal symptoms. Second, HRV and Yangdorak diagnosis were measured in both groups. Results : 1. The FD group in this study mainly had the complaint of 'bloating' symptoms. 2. There was statistically no significant difference between Yangdorak (total average and 24 acupoints) and HRV values except logarithmic low-frequency band (lnLF) and total power (TP) in frequency domain. 3. There was statistically no significant relationship between HRV and Yangdorak in either group. However, most Yangdorak values were positively related with some HRV values (low-frequency, low-frequency/high-frequency ratio and high-frequency, etc) in the control group. Conclusions : FD patients had relatively lesser sympathetic domain than healthy subjects, indicated by decreased lnLF and TP. Particularly, there were positive relationships and significant differences between Yangdorak and HRV in young healthy subjects. This suggests that biosignals from HRV may be a useful method that can differentiate FD from healthy state in those of young age.

• Clinical and Experimental Pediatrics
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• v.62 no.11
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• pp.416-421
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• 2019

Background: The seropositivity rate of hepatitis B surface antigen (anti-HBs) antibodies is known to be ≥95% after hepatitis B virus vaccination during infancy. However, a low level or absence of anti-HBs in healthy children is discovered in many cases. Recent studies in adults reported that a reduced anti-HBs production rate is related to obesity. Purpose: To investigate whether body mass index (BMI) affects anti-HBs levels in healthy children following 3 serial dose vaccinations in infancy. Methods: We recruited 1,200 healthy volunteers aged 3, 5, 7, or 10 years from 4-day care centers and 4 elementary schools. All subjects completed a questionnaire including body weight, height, and vaccine type received. Levels of serum hepatitis B surface antigen (HBsAg) and anti-HBs in all subjects were analyzed using electrochemiluminescence immunoassay. The standardized scores (z score) for each sex and age were obtained using the lambda-mu-sigma method in the 2017 Korean National Growth Charts for children and adolescents. Results: Our subjects (n=1,200) comprised 750 males (62.5%) and 450 females (37.5%). The overall anti-HBs seropositivity rate was 57.9% (695 of 1,200). We identified significant differences in mean BMI values between seronegative and seropositive groups (17.45 vs. 16.62, respectively; P<0.001). The anti-HBs titer was significantly decreased as the BMI z score increased adjusting for age and sex (B=-15.725; standard error=5.494; P=0.004). The probability of anti-HBs seropositivity based on BMI z score was decreased to an OR of 0.820 after the control for confounding variables (95% confidence interval, 0.728-0.923; P=0.001). Conclusion: There was a significant association between anti-HBs titer and BMI z score after adjustment for age and sex. Our results indicate that BMI is a potential factor affecting anti-HBs titer in healthy children.

• 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.

• The Journal of Korean Medicine
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• v.42 no.2
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• pp.50-61
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• 2021

Objectives: The object of this study was to examine whether there was a significant difference between morning and afternoon in heart rate variability(HRV) in healthy Korean adults. In addition, the correlation between the characteristics of the subjects and the test results was analyzed. Methods: From January 8, 2021 to January 29, 2021, twenty healthy subjects received short-term HRV test once in the morning(6:00~12:00) and twice in the afternoon(12:00~18:00). We used IBM SPSS Statistics 27 to test for statistical significance. Results: The mean heart rate and PSI decreased significantly and SDNN increased significantly in the morning compared to the afternoon. There was no significant difference except RMSSD in HRV conducted at 2 hours intervals in the afternoon. Age had a significant difference in SDNN and TP, and exercise in average heart rate. Age, weekly exercise frequency, and monthly drinking frequency showed significant correlations with HRV indicators. As a result of multiple regression analysis, monthly drinking frequency was a variable that had a significant influence on TP. Conclusions: The results of the tests performed with short interval were relatively consistent, and when comparing the results of the afternoon and the next morning, there were significant differences in several indicators. In the future, the number of HRV measurements should be increased and a larger-scale follow-up study including more subjects will be needed.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.2
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• pp.153-164
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• 2024

This study aimed to identify metabolic biomarkers and investigate changes in intestinal microbiota in the feces of healthy participants following administration of Lactococcus lactis GEN-001. GEN-001 is a single-strain L. lactis strain isolated from the gut of a healthy human volunteer. The study was conducted as a parallel, randomized, phase 1, open design trial. Twenty healthy Korean males were divided into five groups according to the GEN-001 dosage and dietary control. Groups A, B, C, and D1 received 1, 3, 6, and 9 GEN-001 capsules (1 × 10¹¹ colony forming units), respectively, without dietary adjustment, whereas group D2 received 9 GEN-001 capsules with dietary adjustment. All groups received a single dose. Fecal samples were collected 2 days before GEN-001 administration to 7 days after for untargeted metabolomics and gut microbial metagenomic analyses; blood samples were collected simultaneously for immunogenicity analysis. Levels of phenylalanine, tyrosine, cholic acid, deoxycholic acid, and tryptophan were significantly increased at 5-6 days after GEN-001 administration when compared with predose levels. Compared with predose, the relative abundance (%) of Parabacteroides and Alistipes significantly decreased, whereas that of Lactobacillus and Lactococcus increased; Lactobacillus and tryptophan levels were negatively correlated. A single administration of GEN-001 shifted the gut microbiota in healthy volunteers to a more balanced state as evidenced by an increased abundance of beneficial bacteria, including Lactobacillus, and higher levels of the metabolites that have immunogenic properties.

• Journal of Acupuncture Research
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• v.29 no.4
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• pp.43-53
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• 2012

Objectives : This study was accomplished to investigate the effects of moxibustion at Jeonjung($CV_{17}$) on the heart rate variability(HRV) in healthy adults. And based on that, we tried to find out how moxibustion at Jeonjung($CV_{17}$) effects on the activity and balance of the autonomic nervous system Methods : We investigated on 50 healthy volunteers consisted of 24 subjects in moxibustion group and 24 subjects in control group. On the other hand, two volunteers were ruled out by standard of elimination. The study was established by randomized trial. Moxibustion was applied at Jeonjung($CV_{17}$) and rested during 10 minutes in moxibustion group. No treatment was executed in control group. We measured HRV 3 times : baseline measurement and after treatment in moxibustion group(after rest in control group) twice. The SPSS 12.0 for windows was used to analyze the data by paired t-test, Wilcoxon signed ranks test(in group) and Independent t-test, Mann-Whitney U-test (between the groups). Results : 1. In moxibustion group, mean HRT decreased significantly. Ln(VLF) increased significantly. Ln(TP) decreased significantly at $2^{nd}$ time and increased significantly at $3^{rd}$ time. SDNN, RMSSD, PSI, Ln(LF), Ln(HF), Normalized LF, Normalized HF and LF/HF ratio were not affected. 2. In control group, PSI and normalized HF decreased significantly. SDNN, Ln(TP), Ln(VLF), normalized LF and LF/HF ratio increased significantly. Mean HRT, RMSSD, Ln(LF) and Ln(HF) were not affected. Conclusions : This study suggest that moxibustion at Jeonjung($CV_{17}$) makes no effects on the balance of the autonomic nervous system.

• Journal of Acupuncture Research
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• v.28 no.2
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• pp.13-25
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• 2011

Objectives : This study was accomplished to investigate the effects of acupuncture at Jeonjung($CV_{17}$) on the heart rate variability(HRV) in healthy adults. And based on that, we tried to find out how acupuncture at Jeonjung($CV_{17}$) effects on the activity and balance of the autonomic nervous system. Methods : We investigated on 74 healthy volunteers consisted of 24 subjects in acupuncture group, 24 subjects in sham acupuncture group and 24 subjects in control group. On the other hand, two volunteers were ruled out by standard of elimination. The study was established by randomized trial. Acupuncture was applied at Jeonjung($CV_{17}$) during 10 minutes in acupuncture group and minimal acupuncture was applied at the same area in sham acupuncture group. No treatment was executed in control group. We measured HRV 3 times : baseline measurement and after treatment in acupuncture group and sham acupuncture group (after rest in control group) twise. The SPSS 15.0 for Windows was used to analyze the data by paired t-test, Wilcoxon signed ranks test (in group) and One-Way ANOVA, Kruskal-Wallis test (between the groups). Results: 1. In acupuncture group, Mean HRT, PSI, Normalized HF decreased significantly. SDNN, Ln (TP), Ln (LF), Ln (VLF), Normalized LF and LF/HF ratio increased significantly. RMSSD, Ln(HF) were not affected. 2. In sham acupuncture group, all indicators were not affected. 3. In control group, mean HRT, Ln(TP) decreased significantly. SDNN, RMSSD, PSI, Ln(LF), Ln(HF), Ln(VLF), normalized LF, normalized HF and LF/HF ratio were not affected. Conclusions : We suggest that acupuncture at Jeonjung($CV_{17}$) increases the activity of autonomic nervous system and makes effects on the balance of the autonomic nervous system.

• The Journal of Korean Physical Therapy
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• v.25 no.6
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• pp.374-378
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• 2013

Purpose: Human body have biological rhythmic pattern in a day, which is affected by internal and external environmental factors. We investigated whether respiratory function was fluctuated according to the influence of time-of-day (around at 9 am, 1 pm, and 6 pm) in health subjects, using pulmonary function test (PFT). Methods: Eighteen healthy volunteers (8 men, mean ages; $22.4{\pm}1.6$, mean heights; $166.61{\pm}9.60$, mean weight; $59.3{\pm}10.3$) were recruited. Pulmonary function test (PFT) was measured at three time points in day, around 9 am, 1 pm, and 6 pm in calm research room with condition of under 55dB noise level, using a spirometer (Vmax 229, SensorMecis, USA). Forced vital capacity (FVC), forced expiratory volume at one second (FEV1), FVC/FEV1, and peak expiratory flow (PEF) were acquired. Results: In comparison of raw value of PFT among three time points, subjects showed generally better respiratory function at 9 am, than at other points, although no significance was found. In comparison of distribution of ranking for respiratory function in each individual, only PEF showed significant difference. In general, distributional ratio of subjects who showed best performance of respiratory function in a day was high. Conclusion: These findings showed that circadian rhythm by diurnal pattern was not detected on respiratory function throughout all day. But, best performance on respiratory function was observed mostly in the morning, although statistical significance did not exist.