Cognition enhancing effect of panax ginseng in Korean volunteers with mild cognitive impairment: a randomized, double-blind, placebo-controlled clinical trial

This study aimed to investigate the cognition-enhancing effect of Panax ginseng. A randomized, double-blind, placebo-controlled clinical trial was conducted to address the cognition-enhancing effects of Panax ginseng. A total of 90 Korean volunteers with mild cognitive impairment participated in this study. All subjects were allocated randomly into ‘Ginseng’ group or ‘Placebo’ group. All subjects were administered 3g of Panax ginseng powder or starch (placebo) for 6 months. The Korean version of the Mini-Mental Status Examination (K-MMSE), Korean version of Instrumental Activities of Daily Living (K-IADL), and Seoul Neuropsychological Screening Battery (SNSB) were used to assess the changes in cognitive function at the end of the 6 month study period. The subjects of the ‘Ginseng’ group improved significantly on the Rey Complex Figure Test (RCFT) immediate recall (P = 0.0405 and P = 0.0342 in per-protocol (PP) and intention-to-treat (ITT) analysis, respectively) and on the RCFT 20-min delayed recall (P = 0.0396 and P = 0.0355 in PP and ITT analysis, respectively) compared with ‘placebo’ group throughout the 6 months of Panax ginseng administration. There were no serious adverse events. These results suggest that Panax ginseng has a cognition-enhancing effect.

Screening study for genetic polymorphisms affecting pharmacokinetics of talniflumate

Talniflumate is a phthalidyl ester of niflumic acid, which has potent analgesic and anti-inflammatory effects and is widely used to treat inflammatory disorders, such as rheumatoid arthritis. To screen the possible genetic factors affecting the pharmacokinetics (PK) of talniflumate, 23 male Korean volunteers were enrolled from two separate bioequivalence studies. All subjects received 740 mg (two tablets) talniflumate in a standard 2×2 cross-over model in a randomized order. For the genetic study, PK parameters of the reference drug were used. We used Illumina Human610Quad v1.0 DNA Analysis BeadChip for whole genome single nucleotide polymorphism (SNP) analysis and whole genome genotyping data were processed by linear regression analysis for PK parameters. Whole genome analysis revealed 1498 significant SNPs (P < 0.0001) for Cmax, 65 significant SNPs (P < 0.0001) for T(max), and 1491 significant SNPs (P < 0.0001) for AUC(inf). For clinical pharmacological purposes, we selected SNPs from drug metabolizing enzymes and transporters, and analyzed the PK parameters of various genotypes. Two SNPs (rs11165069 from ABCA4 (p=0.00002); rs17847036 from CYP2C9 (p=0.000001)) showed significant associations with talniflumate C(max). In the T(max) group, two SNPs (rs3787555 from CYP24A1 (p=0.00035); rs2275034 from ABCA4 (p=0.000587)) showed significant associations with talniflumate T(max). In the AUC(inf) group, two SNPs (rs11165069 from ABCA4 (p=0.00002); rs12461006 from SLC1A6 (p=0.00008)) exhibited significant associations with talniflumate absorption. These results show that genetic factors could affect the PK parameters, and provide information that may be used in the development of personalized talniflumate therapy.

Comparative pharmacokinetic and tolerability evaluation of two simvastatin 20 mg formulations in healthy Korean male volunteers

Simvastatin is used to reduce plasma cholesterol by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and is primarily used to treat hypercholesterolemia. This study was conducted to assess the bioequivalence between the generic formulation of simvastatin 20 mg and the branded formulation of simvastatin 20 mg. A generic formulation of simvastatin 20 mg tablet was developed and the pharmacokinetics of the generic formulation were compared with those of the branded formulation of simvastatin 20 mg tablet in 33 healthy male volunteers after a single oral dose in a randomized, open-label, two-period, two-sequence, crossover study. The reference (Zocor®, MSD Korea LTD.) and test (Simvarotin®, Korea Arlico Pharm Co., Ltd.) formulations, two 20 mg tablets each, were administered to all subjects in fasting status. The serial blood samples for pharmacokinetic analysis were collected before dosing and up to 24 hours post-dose, and plasma concentrations of simvastatin were determined by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters including T(max), C(max), AUC(last), AUC(inf) and t½ were calculated for both formulations by non-compartmental method, and the log-transformed C(max) and AUC(last) were compared statistically. Geometric mean ratios (90% confidence intervals) of the test to the reference formulation in C(max) and AUC(last) were 0.9652 (0.8302–1.1223) and 0.9891 (0.8541–1.1455), respectively. No significant differences in tolerability profiles were noted between the two formulations. The two formulations of simvastatin 20 mg tablets exhibited comparable pharmacokinetic profiles and 90% confidence intervals were within the acceptable range of bioequivalence criteria.

Screening study for genetic polymorphisms affecting pharmacokinetics of simvastatin

Simvastatin reduces plasma cholesterol by inhibiting HMG-CoA reductase (HMGR) and is widely used in the treatment of hypercholesterolemia. To screening the possible genetic factors affecting the pharmacokinetics (PK) of simvastatin, 35 male Korean volunteers were enrolled from two separate bioequivalence studies. Each subject was administered 20 mg simvastatin and reference drug PK parameters were used. We used Illumina Human610Quad v1.0 DNA Analysis BeadChip for whole genome SNPs analysis and whole genome genotyping data was processed by linear regression analysis for PK parameters of drug metabolizing enzymes and transporters. We found 145 significant SNPs (P < 0.01) in C(max), 135 significant SNPs (P < 0.01) in T(max) and 85 significant SNPs (P < 0.01) in AUC(inf) from whole genome analysis. In particular, we found that the ABCC2 gene had a significant effect on C(max) and AUC(inf). These results could provide information of possible candidate genes for personalized simvastatin therapy.

Pharmacokinetic comparison of two levofloxacin 100-mg tablet formulations and determination of time point appropriately reflecting its area under the curve

Levofloxacin is a broad-spectrum antibiotic with activity against gram-positive and -negative bacteria. This study compared the pharmacokinetics (PK) and evaluated the bioequivalence of two levofloxacin 100-mg tablet formulations. An open, randomized, two-way crossover study was conducted in 28 healthy volunteers. The reference (Cravit Tab 100-mg, Jeil) or test (Levobacter Tab, Seoul) formulation was administered and serial blood samples were collected over 24 h for PK analysis. Levofloxacin plasma concentrations were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The correlation of levofloxacin concentration at various time points with the area under the concentration time-curve over the time interval from 0 extrapolated to infinity (AUCinf) was estimated to determine the best reflected time point. The average half-life, maximum plasma concentration (Cmax), and AUClast were comparable. The 90% confidence intervals (CIs) of the geometric mean ratio (GMR test/reference) of AUClast and Cmax were 0.8200-1.0633 and 0.9474-1.0643 respectively. Both formulations were tolerated with no clinically relevant safety issues. Plasma levofloxacin concentrations at various time points correlated well with the AUCinf, and showed high correlation coefficients (r > 0.7, P < 0.001) for both drugs 8 and 12 h after administration. Both formulations showed similar PK profiles while levofloxacin plasma levels after administration indicated their bioequivalence. The Cmax and AUClast GMR 90% CIs were 0.80-1.25. Moreover, 12 h was the best time point to predict the AUCinf and therefore suitable for therapeutic drug monitoring.

Erratum: Pharmacokinetics and bioequivalence of two different 20 mg olmesartan tablets: A randomized, single-dose, two-period crossover study in healthy Korean male volunteers

In the published version of this article, an error in the sponsor's identity was discovered in the acknowledgment section.

Screening study for genetic polymorphisms affecting pharmacokinetics of pioglitazone

Pioglitazone is known to have antidiabetic effects through decreasing peripheral, hepatic and vascular insulin resistance by the stimulation of PPAR gamma. To address the possible genetic factors affecting the pharmacokinetics (PK) of pioglitazone, 27 male Korean volunteers were enrolled from two separate bioequivalence studies. Each subject was administered 15 mg pioglitazone and reference drug PK parameters were used. We used Illumina Human610 Quad v1.0 DNA Analysis BeadChip for whole genome SNPs analysis and whole genome genotyping data was processed by linear regression analysis for PK parameters. We found 35 significant SNPs (P < 0.0001) in C(max), 1,118 significant SNPs (P < 0.0001) in T(max) and 1,259 significant SNPs (P < 0.0001) in AUC(inf) from whole genome analysis. For clinical pharmacological purpose, we selected SNPs from several phase I and II drug metabolizing enzyme and analyzed PK parameters with genotypes. Four SNPs (rs7761731 and rs3799872 from CYP39A1; rs156697 from GSTO2; rs1558139 from CYP4F2) showed significant associations with pioglitazone C(max). In the T(max) group, seven SNPs from 3 genes (rs3766198 from CYP4B1; rs2270422 from GSTZ1; rs2054675, rs10500282, rs3745274, rs8192719, and rs11673270 from CYP2B6) had significant associations. In the AUC(inf) group, seven SNPs from 4 genes (rs11572204 from CYP2J2; rs4148280 from UGT2A1, rs4646422 from CYP1A1; rs3745274, rs8192719, rs11673270, and rs707265 from CYP2B6) showed significant associations with pioglitazone absorption. These results showed that genetic makeup could affect the PK parameters and these informations could be provide information for personalized pioglitazone therapy.

Effects of Customized Nutritional Education 'Change 10 Habits' Program According to Stage of Behavior Change in Mildly Obese Adults

The prevalence of obesity is increasing worldwide and has become a serious epidemic health problem. We developed the 'Change 10 Habits' educational program based on obesity treatment and dietary guidelines and examined its effects on customized nutrition education in mildly obese adults. The study was approved by the Institutional Review Board. Study subjects were excluded if they had several major diseases, if had consumed an anti-obesity drug, or if they practiced an obesity-related program within 30 days. The subjects (n=87, 25< or = BMI<30) were each exposed to the customized nutrition education program with four lessons according to the stage of the transtheoretical model (TTM). The stage-matched program was administered for 12 weeks and was run by a clinical dietitian. Overall, subjects who were in the precontemplation/contemplation stage at baseline made progress in the preparation and action/maintenance stage after 12 weeks (P<0.05). For 'Alcohol is consumed, up to 2 drinks per day', the proportion of subjects who belonged in the action/maintenance stage increased from 34.5% to 49.4% at 12 weeks. In addition, scores of all items significantly increased after the program (P<0.05). 'Chew more than 10 times and eat slowly' score significantly increased from 3.9+/-2.4 to 5.8+/-2.3 (P<0.05). In conclusion, behavioral stage-matched nutrition education using the 'Change 10 Habits' program was effective in improving eating behaviors and enhancing healthy lifestyles in mildly obese adults.

Bioequivalence of the pharmacokinetics between two formulations of 0.2 mg tamsulosin hydrochloride in healthy subjects

Tamsulosin is an effective therapeutic option for lower urinary tract symptoms, as it selectively blocks alpha1A- and alpha1D-adrenoceptors in the bladder and prostate. The purpose of this study was to evaluate the bioequivalence in the pharmacokinetics (PK) of two 0.2 mg tamsulosin formulations when administered as the reference formulation (Yuropa(R) sustained-release tablet) vs. the test formulation (Yutanal(R) capsule) in healthy male subjects. A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 37 healthy volunteers. The 0.2 mg of tamsulosin as the test or the reference formulation were administered during each period, and serial blood samples were collected up to 36 hours after dosing for PK analyses. A non-compartmental analysis was used to estimate the PK parameters. Geometric mean ratios (GMR) and 90% confidence inter-vals (CIs) were calculated for the two formulations to compare the maximum concentration (Cmax) and the area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast). The mean Cmax and AUClast for the test formulation were 6.19 microg/L and 71.30 microg.h/L, respectively, and 5.76 microg/L and 70.38 microg.h /L for the reference formulation, respectively. The GMRs (90% CIs) of the Cmax and AUClast between the two formulations were 1.09 (1.01-1.17) and 1.03 (0.96-1.10), respectively. Tamsulosin 0.2 mg as the test formulation exhibited bioequivalent PK profiles to those of the reference formulation. Therefore, the test formulation is expected to be an alternative to the reference formulation without concerns about differences in drug exposure.

Bioequivalence study of Donepezil hydrochloride in healthy Korean volunteers

Donepezil is a centrally acting, reversible acetylcholinesterase inhibitor that is widely used for treating Alzheimer's disease. This study aimed to compare the pharmacokinetics of Bastia(R), a test tablet formulation of donepezil hydrochloride 10 mg, with those of Aricept(R), the reference tablet formulation of donepezil hydrochloride 10 mg, in healthy Korean male volunteers. A randomized, single-dose, two-way crossover study was conducted in 32 subjects. Subjects received a single dose of either test or reference compound and the alternate drug after a 4-week washout period. Serial blood samples for pharmacokinetic analysis were collected prior to dosing and periodically for 288 h after dosing for measurement of the plasma concentrations of donepezil. A non-compartmental method was used to estimate the pharmacokinetic parameters. The maximum concentration (C(max)) and the area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC(288h)) for the two formulations were compared to evaluate bioequivalence. The C(max) of the test and reference drugs were 27.58+/-7.46 and 26.35+/-6.51 microg/L (mean+/-SD), respectively, while AUC(288h) was 1080.14+/-229.77 and 1043.07+/-242.28 microg.h/L (mean+/-SD), respectively. The geometric mean ratios (90% confidence interval) of the C(max) and AUC(288h) of the two tablets were 1.043 (0.990-1.099) and 1.039 (1.013-1.065). In conclusion, the newly formulated tablet of donepezil hydrochloride 10 mg is bioequivalent to the currently marketed 10 mg tablet.

Pharmacokinetics and bioequivalence of two different 20 mg olmesartan tablets: A randomized, single-dose, two-period crossover study in healthy Korean male volunteers

Olmesartan is an angiotensin receptor blocker (ARB) and is widely used in clinical practice to treat hypertension. To compare the pharmacokinetic (PK) parameters and tolerability of two oral formulations of olmesartan (test drug: OMETAN(R) 20 mg tablet, reference drug: OLMETEC(R) 20 mg tablet) and assess their bioequivalence, a randomized, single dose, two-treatment crossover clinical study was conducted. At each period, 40 subjects received the test drug or the reference drug. Blood samples were collected at pre-dose and up to 48 h after study drug administration of each period. Plasma concentrations of olmesartan were measured using liquid chromatography-tandem mass spectrometry. To evaluate PK profiles, maximum plasma concentration (C(max)) and area under the concentration-time curve from zero to last measurable time (AUC(last)) were estimated using a non-compartmental method. Tolerability was evaluated based on the incidence of adverse events, vital signs, electrocardiograms, and laboratory tests. A total of 39 subjects completed the study. The geometric mean ratio and 90% confidence intervals (CI) of test drug to reference drug were 1.027 (0.969-1.088) for C(max) and 1.014 (0.957-1.074) for AUC(last), respectively. There were no serious adverse events and both formulations of olmesartan were well tolerated. The OMETAN 20 mg tablet was judged to be bioequivalent to the OLMETEC 20 mg tablet.

A Case of Relapsing Polychondritis with Sequentially Bilateral Sudden Sensory Neural Hearing Loss / 대한이비인후과학회지

Relapsing polychondritis is a relatively rare systemic disease of unknown etiology. The disease is considered as an autoimmune disorder and characterized by episodic recurrent inflammation of cartilage and connective tissue, most often of the ears, nose, eyes, joints, respiratory tract, cardiovascular system and audiovestibular system. Treatment plans involve suppression of the immune system with corticosteroid. However, steroid therapy is associated with a number of adverse effects, and non-steroidal anti-inflammatory agents and immunosuppressive agents are helpful in treating the disease. Authors have recently experienced a case of relapsing polychondritis in a 24-year-old man who had both auricular chondritis and bilateral sudden hearing loss with vertigo. The patient showed a significant hearing improvement with the treatment using steroid and immunosuppressive agents. We report this case with a review of the literature.

A bioequivalence study of two levofloxacin tablets in healthy male subjects

Levofloxacin is a bactericidal broad spectrum antibiotic against Gram-positive and Gram-negative pathogens. A randomized, two-treatment, two-period, two-way crossover study was conducted to evaluate the bioequivalence of Lectacin 250 mg tablet, a generic levofloxacin, to its reference drug, Cravit 250 mg tablet. Each period was separated by a 7-day washout. Serial blood samples were collected until 24 h after dosing and plasma levofloxacin concentrations were determined using a high performance liquid chromatography. Pharmacokinetic parameters were analyzed using K-BE Test 2007 and BA calc 2007 (Ministry of Food and Drug Safety, Cheongju-si, South Korea). The peak concentration (Cmax) and the area under the plasma concentration versus time curve from 0 to the last measurable concentration (AUC(0-t)) for the generic and reference levofloxacin were 4.48+/-0.89 mg/L and 4.46+/- 0.95 mg/L, and 25.33+/-4.12 mg*h/L and 25.77+/-4.01 mg*h/L, respectively, leading to a geometric mean ratio (90% confidence interval) of the generic to the reference levofloxacin of 1.0060 (0.9339-1.0842) and 0.9810 (0.9476-1.0159), respectively, for Cmax and AUC(0-t). Lectacin 250 mg tablet is bioequivalent to Cravit 250 mg tablet.

A Large Dentigerous Cyst Found in the Mandible

Dentigerous cysts are benign odontogenic cysts that are associated with the crowns of permanent teeth. They are developmental epithelial-lined lesions which are formed from fluid accumulation in the space between the reduced enamel epithelium and the surface of crown. This may occure due to the obstructin of venous return caused by tooth impaction. The most prevalent location of dentigerous cysts are the third molar of mandible. While the single dentigerous cysts are the second most common odontogenic cysts following the radicular cysts of jaw, multiple cysts are observed in patients with some conditions such as mucopolysaccharidosis type IV, basal cell nevus syndrome, and cleidocranial dysplasia. They occur in young patients in the second or third decades of life, but it is a rare occurrence for children. A sixteen-year-old girl with painful swelling in the right mandible visited to our department. All routine laboratory test results were within normal limits. However, we were able to diagnose that she had facial asymmetry. Computed tomography showed a well-defined soft tissue mass obliterating right mandible ramus with an impacted tooth. We performed total enucleation of cyst and molar tooth. The pathology revealed a non-keratinized squamous epithelial lined cyst associated with an undamaged tooth.

Pharmacokinetics, Pharmacodynamics and Safety of JES9501 after Single and Multiple Oral Administration in Healthy Subjects

BACKGROUND: JES9501 is dehydroevodiamine, the extract of Evodia rutaecarpa, expected to be a new therapeutic for Alzheimer disease. This study aims to investigate the pharmacokinetics (PK), pharmacodynamics (PD) and safety of JES9501 after single or multiple dosing. METHODS: A double-blind, randomized, placebo-controlled, dose ascending, parallel study was conducted in healthy subjects. A single dose of JES9501 50.100.200.400 or 800 mg and multiple doses of JES9501 100.200 or 400 mg once-daily for 7days was administered. Serial blood and urine samples for PK evaluation were collected. Acetylcholinesterase (AChE) activity was measured for PD evaluation in multiple dose group. RESULTS: In the single dose study, means of dose-normalized peak concentration (Cmax) of 100.200.400 and 800 mg dose group are comparable except 50 mg dose group. Means of dose-normalized area under the plasma concentration-time curve (AUC) from dosing to the last quantifiable concentration of corresponding dose group were similar. At steady state in the multiple dose study, means of dose-normalized Cmax and AUC for dosing interval of 100.200 and 400 mg dose group decreased as the dose increased, however those were not relevant. There was no significant difference of AChE activity between three dosage groups and placebo group. Adverse events related to study drug were all mild and there were no remarkable findings. CONCLUSION: JES9501 was safe and well-tolerated after single or multiple doses in healthy male subjects. Further studies are warranted to evaluate the PK of optimized dosage form and to prove the drug effect in clinical trials for Alzheimer disease patients.

Pharmacokinetics of T-614 after Single Oral Administration in Healthy Korean Volunteers

BACKGROUND: Iguratimod is a new type of disease modifying anti-rheumatic drug, which reduced the production of inflammatory cytokines. The purpose of this study was to evaluate pharmacokinetic characteristics and safety profiles of iguratimod after a single oral administration in healthy Korean volunteers. METHODS: A randomized, double-blind, placebo-controlled, parallel group, single oral dose study was conducted in 24 healthy male volunteers. Three groups of eight subjects each received 25 mg, 50 mg, or 100 mg dosage, respectively. Two subjects in each dose group were administered matching placebo. Plasma concentrations of iguratimod were measured till 72 hours after drug administration. Tolerability was evaluated by monitoring adverse events, clinical laboratory tests, and 12-lead electrocardiograms. RESULTS: The mean area under the concentration-time curve from 0 to 72 hours (AUClast) were 11.9, 25.2, and 51.8 mg x h/L and the maximum plasma concentration (Cmax) were 1.15, 2.33, and 4.78 mg/L in 25, 50 and 100 mg dose groups, respectively. All doses of iguratimod were well tolerated without serious adverse events or clinically meaningful changes. CONCLUSION: Cmax and AUClast values of iguratimod proportionally increased with incremental dose. Iguratimod was generally safe and well tolerated.

Use of Triamcinolone-Impregnated Nasal Packing Following Endoscopic Sinus Surgery

OBJECTIVES: To investigate the effectiveness of steroid-impregnated absorbable nasal dressing on wound healing and surgical outcomes after endoscopic sinus surgery (ESS). MATERIALS AND METHODS: Chronic rhinosinusitis patients with nasal polyps who were to undergo bilateral ESS were recruited and randomized to receive triamcinolone-impregnated bioresorbable dressing (Nasopore(R); Polyganics, Groningen, Netherlands) in one nasal cavity and saline-impregnated dressing contralaterally. Postoperative healing assessments of edema, crusting, secretions, and scarring were done at postoperative days 7, 14, and 21 and at 1 and 3 months using validated Lund-Kennedy scores. RESULTS: Analysis of the 20 enrolled patients who completed observation showed no significant difference in Lund-Kennedy scores between the preoperative cavity scores. There was, however, a statistically significant difference in Lund-Kennedy scores of the treatment and control groups at days 7 and 14 (P =0.005 and P=0.0039, respectively), and a significant difference in Lund-Kennedy scores was also detected between the groups at the 3-month time point (P =0.042). CONCLUSION: The results of the data analysis suggest a significant improvement in early postoperative healing and improved healing for up to 3 months postoperatively in nasal cavities receiving triamcinolone-impregnated absorbable nasal packing following ESS.

Cervicofacial Emphysema and Pneumomediastinum Following Pediatric Adenotonsillectomy

Many patients regard tonsillectomy as a minor operation because it is performed frequently. Although tonsillectomy is considered a relatively safe surgical procedure, numerous complications have been described. The common complications are hemorrhage, infection, and following anesthesia, aspiration, cardiac arrhythmia, and laryngeal trauma. Cervicofacial emphysema and pneumomediastinum are rarely observed sequelae of surgical intervention in the upper aerodigestive tract. Although these complications resolve spontaneously in most cases, a few cases result in tension pneumothorax and other life-threatening conditions. Symptoms include chest pain, neck pain, dyspnea and odynophagia. Treatment involves frequent assessment of the airway and extent of the emphysema. The authors of the present study report of a patient who developed pneumomediastinum shortly after an adenotonsillectomy as well as a review of the related literature.

Influence of Simvastatin on Pharmacokinetics/Pharmacodynamics of Aspirin after Oral Co-administration in Healthy Volunteers

BACKGROUND: Both aspirin and simvastatin are prescribed as treatments or prevention of cardiovascular diseases. The aim of this study was to investigate the influence of simvastatin on pharmacokinetics and pharmacodynamics of aspirin after oral co-administration in healthy subjects. METHODS: Subjects were orally administered aspirin 100 mg for 7 days followed by co-administration of aspirin 100 mg and simvastatin 40 mg for 7 days once daily. A series of blood samples were collected before and till 24hours after drug administration on Day 1 (single-dose of aspirin), Day 7 (multiple-dose of aspirin) and Day 14 (multiple-dose of aspirin and simvastatin). The effects of simvastatin on pharmacokinetics of acetylsalicylic acid and salicylic acid were assessed with the 90 % confidence intervals (CIs) of thegeometric mean ratios (GMRs) of Day 14 over Day 7 for maximum plasma concentration (Cmax) and the area under the concentration-time curve (AUC0-24). Pharmacodynamics was assessed with maximal changes of platelet aggregation from baseline. RESULTS: Twenty-fourhealthy men aged 20 to 36 years were enrolled and 23 of them completed the study. GMRs (90 % CIs) of Cmax and AUC0-24 for acetylsalicylic acid were 1.21 (1.04 - 1.42) and 1.28 (1.19 - 1.38), respectively. For salicylic acid, GMRs of Cmax and AUC0-24 were 0.96 (0.91 - 1.00) and 1.00 (0.97 - 1.04), respectively. Maximal changes of platelet aggregation on Day 7 and Day 14 from baseline were not significantly different (p=0.41); 87.5 +/- 8.8 % and 87.3 +/- 9.2 %, respectively. CONCLUSION: Coadministration of simvastatin slightly increased the systemic exposure of acetylsalicylic acid with no changes of systemic exposure of salicylic acid or inhibition of platelet aggregation.

Retraction: Mechanism of Apoptotic Cell Death in Cholesteatoma Epithelium / 대한이비인후과학회지

No abstract available.