No abstract available.
Drug Interactions* ; Metabolism*

Recently, tuberculosis of bone and joint is decreased with good nutrition and environment, development of preventive medicine and improvement of treatment regimen. But it is still one of the common inflammatory diseases in Korea, and must be considered in the differential diagnosis of common orthopedic complaints. There are few reports on extraspinal tuberculosis of bone and joint. Forty one cases of extraspinal tuberculosis of bone and joint were studied in our department from January 1988 to August 1993. The results were as follows; l. Extraspinal tuberculosis of bone and joint were 41 cases (39 patients, 27.8% of 147 tuberculosis of bone and joint including spine). 2. The proportion of children and young adults was 56%, hips were involved in 11 cases, knee joints in 8 cases, ankle joints in 6 cases, feet in 6 cases and elbow joints in 5 cases. 3. Coexisting pulmonary tuberculosis was found in 19 patients and active lesion in 15 patients. 4. Confirmative diagnosis could be made by smear and culture of the lesion or pathologic findings or recently available polymerase chain reaction(PCR) method. 5. Various treatment, such as antituberculous medication, external immobilization, synovectomy, curettage and bone graft, arthrodesis, had been carried out. 6. Reactivation of other site was found in 7.3%(3 cases) and resistant tendency was found in 9.7%(4 cases).
Ankle Joint ; Arthrodesis ; Child ; Curettage ; Diagnosis ; Diagnosis, Differential ; Elbow Joint ; Foot ; Hip ; Humans ; Immobilization ; Joints ; Knee Joint ; Korea ; Methods ; Orthopedics ; Preventive Medicine ; Transplants ; Tuberculosis ; Tuberculosis, Pulmonary ; Young Adult

No abstract available.
Anticonvulsants* ; Drug Interactions*

Pediatric patients with coronavirus disease 2019 (COVID-19) are increasing, and severe cases such as multisystem inflammatory syndrome are being reported. Nafamostat, a repurposing drug, is currently being explored for the treatment of COVID-19 in adults. However, the data supporting its exposure in pediatrics remains scarce. Physiologically-based pharmacokinetic (PBPK) modeling enables the prediction of drug exposure in pediatrics based on ontogeny of metabolic enzymes and age dependent anatomical and physiological changes. The study aimed to establish a PBPK model of nafamostat in adults, then scale the adult PBPK model to children for predicting pediatric exposures of nafamostat and an optimal weight-based nafamostat dose in pediatric population. The developed model adequately described adult exposure data in healthy volunteers following i.v. administration with three doses (10, 20, and 40 mg). Scaling adult PBPK models to five pediatric groups predicted that as age advances from neonate to adult, the exposure of nafamostat slightly increased from neonate to infant, steadily decreased from infant to child, and then increased from child to adult after the administration of 0.2 mg/kg/h for 14 days, a dosing regimen being conducted in a clinical trial for COVID-19. Based on the fold change of predicted area under the curve for the respective pediatric group over those of adults, weight-based dosages for each pediatric group may be suggested. The novel PBPK model described in this study may be useful to investigate nafamostat pharmacokinetics in a pediatric subgroup further.

The mortality and morbidity of peritrochanteric fractures in the elderly are great due to preexisting diseases, the osteoporosis, and poor general conditions. Since the complications sometimes lead to death, it is utmost important to reduce the complications and to prevent them. Authors had experienced 42 peritrochanteric fractures over 65 years old from January, 1988 to December, 1992. Age incidence was distributed from 65 to 93 years. The sites of fractures were 17 femoral neck, 24 intertrochanteric, 1 subtrochanteric. The mortality at postoperative 6 months was 10.2%. The postoperative complications were 6 cardiovascular diseases, 3 pneunonia, 3 pressure sore etc. The results according to interval between injury and operation were not significant, but reducing risk factors following check-up of general conditions was significant. It was necessary in treatment of elderly peritrochanteric fractures to check the general conditions, to reduce risk factors, to choose appropriate method of operation and anesthesia, and to operate as soon as possible by experienced surgeon. Postoperative early ambulation was also significant at good results. The percutaneous pinning under local anesthesia was an recommendable method in patients with severely poor general conditions.
Aged ; Anesthesia ; Anesthesia, Local ; Cardiovascular Diseases ; Early Ambulation ; Femur Neck ; Humans ; Incidence ; Methods ; Mortality ; Osteoporosis ; Postoperative Complications ; Preexisting Condition Coverage ; Pressure Ulcer ; Risk Factors

For the pharmacokinetic analysis of isoniazid transfer into CSF, steady-state isoniazid concentrations of plasma and CSF were measured in eleven tuberculous meningitis patients confirmed with findings of CSF and neuroimazing. Peak plasma levels (4.17-21.5 micrograms/mL) were achieved at 0.25 to 3 hours after multiple isoniazid dose (600 mg/day). Terminal half-life, total clearance (CI/F) and volume of distribution (Vd/F) were 1.42 +/- 0.41 hr, 0.47 +/- 0.22 L/kg/hr and 0.93 +/- 0.48 L/kg, respectively. Isoniazid concentrations in CSF collected intermittently were highest at 3 hr (Mean, 4.18 micrograms/mL) and were 0.54 +/- 0.21 micrograms/mL at 12 hrs after the last dose of isoniazid 10 mg/kg/day. CSF/plasma partitioning of isoniazid and equilibration rate were estimated using modified pharmacokinetic/pharmacodynamic model. Disposition rate constant from CSF to plasma and CSF/plasma partitioning ratio of isoniazid were estimated to be 0.39 h-1 and 1.17, respectively.
Administration, Oral ; Humans ; Isoniazid/*cerebrospinal fluid ; Metabolic Clearance Rate ; Models, Biological ; Tuberculosis, Meningeal/*cerebrospinal fluid

Captopril tablets of two different producers were tested for bioequivalence as well as therapeutic equivalence. The pharmacokinetics, the time course of plasma angiotensin-converting enzyme inhibition, and the changes of systolic and diastolic blood pressure after administration of drugs were studied. In a balanced, randomized two-way crossover design, two single doses of 50mg each of captopril were administered orally to twelve male volunteers. Peak blood levels of free captopril were observed about 0.85 hour after the dose, and practically free captopril could not be detected in blood within 8 hours. Peak free captopril levels of both compounds were almost identical(Capoten(R), 464.3ng/ml ; Capril(R), 504.6ng/ml). No statistically significant difference was identified between two compounds when area und the concentration time curve, peak level, time to peak were compared. Inhibition of plasma angiotensin-converting enzyme to blood free captopril concentration showed the hyperbolic concentration-response relationship with IC50 value of 7.4ng/ml. The area under the percent angiotensin-converting enzyme inhibition versus time curve were quite similar after administration of both drugs. The compounds were also found to be equivalent on the premise that no significant difference was detected when the time courses of systolic and diastolic blood pressure reduction were compared.
Biological Availability* ; Blood Pressure ; Captopril* ; Cross-Over Studies ; Humans ; Inhibitory Concentration 50 ; Male ; Pharmacokinetics ; Plasma* ; Tablets* ; Therapeutic Equivalency ; Volunteers

This study focused on the role of cytochrome P450 2D6 (CYP2D6) genotypes to predict phenotypes in the metabolism of dextromethorphan. CYP2D6 genotypes and metabolic ratios (MRs) of dextromethorphan were determined in 201 Koreans. Unsupervised clustering algorithms, hierarchical and k-means clustering analysis, and color visualizations of CYP2D6 activity were performed on a subset of 130 subjects. A total of 23 different genotypes were identified, five of which were observed in one subject. Phenotype classifications were based on the means, medians, and standard deviations of the log MR values for each genotype. Color visualization was used to display the mean and median of each genotype as different color intensities. Cutoff values were determined using receiver operating characteristic curves from the k-means analysis, and the data were validated in the remaining subset of 71 subjects. Using the two highest silhouette values, the selected numbers of clusters were three (the best) and four. The findings from the two clustering algorithms were similar to those of other studies, classifying *5/*5 as a lowest activity group and genotypes containing duplicated alleles (i.e., CYP2D6*1/*2N) as a highest activity group. The validation of the k-means clustering results with data from the 71 subjects revealed relatively high concordance rates: 92.8% and 73.9% in three and four clusters, respectively. Additionally, color visualization allowed for rapid interpretation of results. Although the clustering approach to predict CYP2D6 phenotype from CYP2D6 genotype is not fully complete, it provides general information about the genotype to phenotype relationship, including rare genotypes with only one subject.
Alleles ; Classification ; Cluster Analysis* ; Cytochrome P-450 CYP2D6* ; Dextromethorphan ; Genotype ; Metabolism ; Phenotype* ; ROC Curve

BACKGROUND: Demands for complicated and long-term administration clinical trials have been increased since investigators actively involved in early stage clinical trials including first-in-human (FIH) trials. Research wards in our clinical trial center were mainly used for phase 1 trials. In order to perform several clinical trials simultaneously during a short period with a minimum number of rooms, beds, and equipment, staffs have to spend a lot of time for efficient operation of limited numbers of facilities. In this study, automated bed-allocation system was developed for efficient scheduling of the research ward based on clinical trial condition and status like experts. METHODS: The system was developed based on clinical trial design, schedule, and the information on research bed and availability stored and updated in database (DB). Automatic assignment system was designed to find an optimal schedule according to the given information using expert rules and algorithms. The optimal solution can be visualized on Gantt chart using C# and Chart FX API. RESULTS: The system was developed to demonstrate the schedule on color chart. It turned out to be well-designed to find an optimal schedule for bed allocation. The system also allows automatic updating of the schedule and information in the DB. CONCLUSION: Automated bed-allocation system developed in this study could save time and improve the efficiency for using space and equipment in clinical trial center. The system can be also applied to similar works or tasks in other fields.
Appointments and Schedules ; Expert Systems ; Humans ; Research Personnel

We developed a high-performance liquid chromatographic procedure for the determination of 4-(4-chlorophenyl)-4-hydroxypiperidine (CPHP), a toxic metabolite of haloperidol, in human. Chromatographic analysis was performed on a reverse-phase C₁₈ column with a mobile phase containing 50 mM potassium phosphate buffer/acetonitrile (75:25, vol/vol) using UV detection with a wavelength of 220 nm. The limits of detection for CPHP were 1 ng/ml in urine and the assay was linear over the concentration range of 2-500 ng/ml for urine. This analytical method was applied to measure CPHP in human. Nineteen healthy subjects were enrolled and all subjects received a single oral dose of 5 mg haloperidol following a treatment of placebo or itraconazole at 200 mg/day for 10 days in a randomized crossover manner. CPHP was detected in urine samples and average recovered amount of CPHP was 81.31 µg/24 hr in the placebo phase and it was significantly reduced to 30.34 µg/24 hr after itraconazole treatment. The finding provides in vivo evidence that CPHP is an in vivo metabolite of haloperidol in human and its formation is mediated by CYP3A4.
Chromatography, High Pressure Liquid ; Cytochrome P-450 CYP3A ; Haloperidol* ; Healthy Volunteers ; Humans* ; Itraconazole ; Limit of Detection ; Methods* ; Potassium