Increasing Source-Object Distance: A Computed Radiographybased Strategy to Reducing Radiation Dose in Occipital-Frontal Skull X-Ray

@#Introduction: Exploring potential optimization strategies and developing evident practices is critical. Previous studies show that radiation dose can be reduced by increasing the source-image distance (SID). Although most studies use digital radiography, many hospitals in underdeveloped countries still use computed radiography (CR). Therefore, research will investigate the relationship between SID and Entrance surface dose (ESD) using the CR. Methods: This study involved the measurement of radiation dose and image quality of a radiological procedure performed at a reference SID; 100cm and the tested SIDs; 110cm, 120cm, and 130cm, using constant technical factors (70kVp, 25mAs, grid). A LiF; Mg Ti thermoluminescence dosimeter (TLD-100) chip was placed in the center of the radiation field of the OF10° skull radiography examination to measure ESD. Image quality was assessed using the European Commission guidelines and graded using relative visual assessment analysis (VGA). Results: Significant ESD reduction from 21% and 45% when SID was increased from 100cm to 130cm (p <0.001), where SID was negatively correlated with ESD (r= - 0.98). The VGA scores showed no statistical difference in the image quality of the OF10° skull radiography examination for the tested and reference images (p=0.21). VGA scores for 120cm images showed the highest image quality among the SIDs tested with a dose reduction of 37%. Conclusion: ESD was statically reduced when SID was increased from 100cm to 130cm, while image quality was diagnostically acceptable. The study suggests that 120cm is the optimal SID when both dose and image quality are considered.

Research Progress in Diagnostic Reference Levels in Interventional Radiology / 中国医学科学院学报

During interventional procedures,subjects are exposed to direct and scattered X-rays.Establishing diagnostic reference levels is an ideal way to optimize the radiation dose and reduce radiation hazard.In recent years,diagnostic reference levels in interventional radiology have been established in different countries.However,because of the too many indicators for characterizing the radiation dose,the indicators used to establish diagnostic reference levels vary in different countries.The research achievements in this field remain to be reviewed.We carried out a retrospective analysis of the definition,establishment method,application,and main factors influencing the dose difference of the diagnostic reference level,aiming to provide a basis for establishing the diagnostic reference level for interventional procedures in China.

Value of generalized equivalent uniform dose optimization in radiotherapy for chest malignant tumors / 中国辐射卫生

Objective To explore the value of generalized equivalent uniform dose (gEUD) optimization in radiotherapy for chest malignant tumors. Methods Sixty patients with chest malignant tumors who were treated in Center for Tumor Radiotherapy, Chizhou Municipal People’s Hospital, Anhui Province, China from October 2021 to June 2022 were enrolled; each patient underwent tumor localization with a conventional fixed computed tomography scan. The patients were divided into two groups using the same field direction and weight in the Varian Eclipse 15.6 planning system. The first group was planned using the conventional physical dose-volume objective function plus the Upper gEUD objective function, with organs at risks (OARs) optimized with the EUD values suggested by the Varian Eclipse 15.6 planning system. The second group only adopted the conventional physical dose-volume objective function for OARs optimization. The two groups were compared for the radiation doses delivered to the OARs. Results Compared with the conventional physical dose-volume objective function alone, the addition of Upper gEUD objective function resulted in no significant difference in lung V5Gy, but resulted in significant reductions in V20Gy and mean dose in the lungs; some reductions in V30Gy, V40Gy, and mean dose in the heart; and significant reductions in the maximum dose in the spinal cord. Conclusion The gEUD objective optimization can effectively protect the normal tissue in the radiotherapy for chest malignant tumors and thus is recommended in radiotherapy planning.

Development of Physiologically Based Pharmacokinetic Model and Assessment of the Impact of Renal Underdevelopment in Preterm Infants on the Pharmacokinetics of Aminophylline

Objective:To develop a physiologically based pharmacokinetic (PBPK) model for individualization of the dosing regimen considering the physiological requirements of these preterm neonates. Methods: The study comprised preterm newborns with fewer than 34 weeks of gestation and six apneic episodes in 24 h. A PBPK model was created using PK-SIM (version 9, update 1, GitHub, San Francisco, CA, USA). A PBPK model is built using a typical loading dosage of 5 mg/kg and a maintenance dose of 1.5 mg/kg. Based on the verified base model, a PBPK model representing renal underdevelopment based on nRIFLE/pRIFLE categorization was developed. Results: The PK parameters of Aminophylline were computed using the PBPK model. As per the model prediction, T1/2 and area under the curve reduced as postnatal age increased, and in the event of renal underdevelopment, even while Cmax for patients under R (RISK), I (injury) was within the therapeutic range; it was greater compared to preterm without any renal complications. Mean Cmax (mol/L) was 59.53 and for R, I, and F (FAILURE) categories the values were 83.04, 99.69, and 126.98, respectively. Conclusion: The model was created using appropriate drug, study subject, and dosage protocol inputs. The established PBPK model could help in individualizing aminophylline dose in preterm babies.

Study of 3D-printed multi-channel applicator in patients treated with brachytherapy after cervical cancer surgery / 中华放射肿瘤学杂志

Objective:To compare the dosimetric difference between 3D-printed multi-channel applicator and conventional vaginal single-channel applicator for brachytherapy, aiming to provide guidance for patients receiving brachytherapy after cervical cancer surgery.Methods:From January 2019 to November 2020, 25 cervical cancer patients complicated with VAIN Ⅲ receiving 192Ir high-dose-rate brachytherapy after cervical cancer surgery were selected. Each patient was located by CT scanning with 3D-printed multi-channel applicator and conventional vaginal single-channel applicator, and corresponding plan and evaluation were carried out. The dose volume histogram (DVH) was obtained by inverse dose optimization algorithm. The dosimetric differences of high-risk clinical target volume (HRCTV), bladder and rectum during brachytherapy were compared with those of source applicators. The optimal treatment plan was selected. Results:D 90%, D 100%, V 100% and V 150% of the plans designed by 3D-printed individual multi-channel applicator had no significant differences compared with those designed by conventional single-channel applicator (all P>0.05). The bladder and rectal D 2cm 3 designed by 3D-printed multi-channel applicator were significantly lower than those using conventional single-channel applicator, and the differences were statistically significant (both P<0.05). Conclusion:The multi-channel individual applicator target made by 3D-printing technology has good conformal property, properly protects the bladder and rectum and possesses treatment advantages over conventional single-channel applicator.

Applications of model-informed drug development (MIDD) on new drug research and development / 中国临床药理学与治疗学

Model-informed drug development (MIDD) refers to the application of various mathematical models in drug development, in order to facilitate the decision-making process. There have been common and mature applications of MIDD to address drug development and regulatory questions in interactional industries and advanced regulatory agencies, especially the US FDA. However, its application in innovative drug development is relatively rare in China. Representative case studies, clinical pharmacology review ex-periences, and relevant guidelines are reviewed in this article to present a preliminary discussion on the main applications of MIDD. Additionally, several suggestions for the application of MIDD in new drug development as well as general considerations for new drug registration are proposed in this paper, for the discussion or reference of industries and researchers.

Application of model-informed drug development approach in dose optimization: Insights from the modification of nivolumab dosage regimen / 中国临床药理学与治疗学

Nivolumab is a humanized monoclonal antibody that blocks the programmed death 1 (PD-1) receptor. The initially recommended dose was 3 mg/kg every 2 weeks (Q2W) when nivolumab was firstly approved by the US FDA in 2014. A flat dose of 240 mg Q2W was approved in 2016, and subsequently 480 mg Q4W in 2018. Model-informed drug development (MIDD) approach was applied for the analyses of drug exposure, safety and efficacy based on the data from existed clinical studies, and the model-informed analyses became the key evidences supporting approval of new dosage regimens. Relevant studies and regulatory considerations related to the nivolumab dose selection and subsequent modification were reviewed in this paper. The application of MIDD approach in dose optimization is additionally discussed.

Evolution and interpretation of diagnostic reference levels for adults undergoing X-ray computed tomography in China / 中华放射医学与防护杂志

The diagnostic reference level (DRL) for adults radiation dose in CT examination based on a large-scale national survey data is released in the form of national health industry standards (WS/T 637-2018) after more than ten years of exploration by radiologists,imaging technologists,radiation protection specialists and radiographers.Its principles and method are in line with international practices and the actual situation in China,which basically cover frequently-used CT examination items for adults.Compared with DRL in several other countries or organizations,radiation exposure to the patients as a whole is at a reasonably low level.The 50th percentile (achievable dosimetry levels) and 25th percentile (indicative level of unusually low dosimetry) are given as additional tools for radiation dose optimization guidance.In daily activities of radiological diagnosis,the radiation dose should be matched with image quality and clinical diagnostic tasks,and the frequency of unjustifiable high or low radiation dose should be reduced.

Evolution and interpretation of diagnostic reference levels for adults undergoing X-ray computed tomography in China / 中华放射医学与防护杂志

The diagnostic reference level (DRL) for adults radiation dose in CT examination based on a large-scale national survey data is released in the form of national health industry standards (WS/T 637-2018) after more than ten years of exploration by radiologists, imaging technologists, radiation protection specialists and radiographers. Its principles and method are in line with international practices and the actual situation in China, which basically cover frequently-used CT examination items for adults. Compared with DRL in several other countries or organizations, radiation exposure to the patients as a whole is at a reasonably low level. The 50th percentile (achievable dosimetry levels) and 25th percentile (indicative level of unusually low dosimetry) are given as additional tools for radiation dose optimization guidance. In daily activities of radiological diagnosis, the radiation dose should be matched with image quality and clinical diagnostic tasks, and the frequency of unjustifiable high or low radiation dose should be reduced.

Pharmacokinetic and pharmacodynamic integration of enrofloxacin against Salmonella Enteritidis after administering to broiler chicken by per-oral and intravenous routes

It is crucial to optimize the dose of fluoroquinolones to avoid antibiotic resistance and to attain clinical success. We undertook this study to optimize the dose of enrofloxacin against Salmonella enterica subsp. enterica serovar Enteritidis (S. Enteritidis) in chicken by assessing its pharmacokinetic/pharmacodynamic (PK/PD) indices. The antibacterial activities of enrofloxacin against S. Enteritidis were evaluated. After administering 10 mg/kg body weight (b.w.) of enrofloxacin to broiler chickens of both sexes by intravenous (IV) and peroral (PO) routes, blood samples were drawn at different intervals and enrofloxacin concentrations in plasma were determined. PK/PD indices were calculated by integrating the PK and PD data. The elimination half-lives (T(1/2)), time required to reach peak concentration (T(max)), peak concentration (C(max)), and area under curve (AUC) after administering enrofloxacin by PO and IV routes were 25.84 ± 1.40 h, 0.65 ± 0.12 h, 3.82 ± 0.59 µg/mL, and 20.84 ± 5.0 µg·h/mL, and 12.84 ± 1.4 h, 0.22 ± 0.1 h, 6.74 ± 0.03 µg/mL, and 21.13 ± 0.9 µg.h/mL, respectively. The bioavailability of enrofloxacin was 98.6% ± 8.9% after PO administration. The MICs of enrofloxacin were 0.0625–1 µg/mL against S. Enteritidis strains, and the MIC₅₀ was 0.50 µg/mL. The C(max)/MIC₅₀ were 7.64 ± 0.2 and 13.48 ± 0.7 and the 24 h AUC/MIC₅₀ were 41.68 ± 0.1 and 42.26 ± 0.3 after administering the drug through PO and IV routes, respectively. The data in this study indicate that the application of 50 mg/kg b.w. of enrofloxacin to chicken through PO and IV routes with a dosing interval of 24 h can effectively cure S. Enteritidis infection, indicating the need for a 5-fold increase in the recommended dosage of enrofloxacin in chicken.

Investigation of radiation dose in CT scanning for adult patients in Ningxia / 中华放射医学与防护杂志

Objective To investigate the current status of CT radiation dose to adults in Ningxia, and provide basic data for developing the first diagnostic reference level of adults from CT scanning. Methods Stratified cluster sampling method was used to investigate the in-service status of CT scanners with various brands and different models in different grades of hospital in Ningxia. Interval sampling method was used to obtain everyday' s scanning parameters and radiation dose values from different types of scanning examinations in surveyed hostipitals. Basic information was collected include hospitals, CT scanner, scanning types and patients. CT scanning parameters, CTDIvol and DLP values were recorded, with effective dose values calculated. The data were statistically analyzed by examination types and comparation was made with the DRL values recommended by other countries. Results Finally, there were 45 medical institutions in this study, including 10 public tertiary A hospitals, 5 public tertiary B hospitals, 23 public secondary A hospitals, 5 private hospitals and 2 physical examination centers. 58 CT scanners from 6 manufacturers and 4952 adult patients were investigated. The 75th percentile (P75) of CTDIvol, DLP, and E values of common scanning examinations were listed as follows: 65.67 mGy, 860.74 mGy·cm, and 1.64 mSv in skull scanning;29.32 mGy, 490. 00 mGy·cm, and 2.83 mSv in neck scanning;36. 92 mGy, 954. 42 mGy·cm, and 4. 87 mSv in neck enhanced scanning; 11. 50 mGy, 382.06 mGy·cm , and 5.68 mSv in chest scanning; 45.80 mGy, 1713.22 mGy·cm, and 25.01 mSv in chest enhanced scanning; 20. 10 mGy, 506. 59 mGy·cm, and 7. 75 mSv in upper abdominal scanning;50. 07 mGy, 1434. 19 mGy·cm, and 21. 94 mSv in upper abdominal enhanced scanning; 14. 33 mGy, 670.78 mGy·cm, and 10. 26 mSv in abdominal-pelvic scanning; 48. 00 mGy, 2294. 00 mGy·cm, and 35.10 mSv in abdominal-pelvic enhanced scanning;16.10 mGy, 471.58 mGy·cm, and 6.08 mSv in pelvic scanning;31.04 mGy, 1138. 78 mGy·cm, and 14. 69 mSv in pelvic enhanced scanning. Conclusions The CT scanning radiation doses to skull, neck, chest and pelvis in Ningxia are slightly lower than, or similar to, in other countries, but the abdominal scanning dose is significantly higher than that in other countries. It is necessary to optimize the abdominal CT scanning protocol.

Evaluation and Optimization of the Dosage Regimens of Lamotrigine for Epileptic Children Based on Monte Carlo Simulation / 中国药学杂志

OBJECTIVE: To estimate and optimize the dosage regimens of lamotrigine for epileptic children with the utilization of Monte Carlo simulation based on the pharmacokinetic/pharmacodynamic principle of antiepileptic drugs. METHODS: Population pharmacokinetic data of lamotrigine for epileptic children in China was obtained from the published literatures. Ten thousand times Monte Carlo simulation were performed for 25 dosing regimens for epileptic children aged 2 to 12 years and 33 dosing regimens for post-12-year-old epileptic children to obtain the steady-state concentration (css) and the probability of target attainment (PTA). Based on this, the rationality of the dosing regimens were evaluated and the optimal dosing regimen was screened. RESULTS: Within the recommended dosage range of lamotrigine for epileptic children aged 2 to 12 years, six of the nine pre-established maintenance-phase regimens were found that the PTA that lamotrigine plateau concentrations distributed in therapeutic window ranged from 80.54% to 90.69%, meanwhile the PTA that plateau concentrations distributed over the therapeutic window ranged from 0.41% to 12.50%, and the predicted mean of css ranged from 4.62 to 9.28 mg•L-1, so each was the optimization regimen. Among the 15 dosage regimens of lamotrigine for epileptic children over 12 years old, eleven of fifteen pre-established maintenance-phase regimens were found that the PTA that lamotrigine plateau concentrations distributed in therapeutic window ranged from 91.51% to 100.00%, the PTA that plateau concentrations distributed over the therapeutic window ranged from 0.00% to 8.49%, and the predicted mean of css ranged from 6.21 to 12.44 mg•L-1, so each was the optimization regimen. Interestingly, five off-label regimens of lamotrigine (12.5, 25, 37.5 mg, bid and 25, 50 mg, qd) in combination with valproic acid were found that the PTA that lamotrigine plateau concentrations distributed in therapeutic window was 100.00%, and the predicted mean of css ranged from 3.84 to 11.51 mg•L-1, which were superior to the recommended dosage (100-200 mg•d-1), indicating use with caution could be acceptable. CONCLUSION: In most cases, lamotrigine can be given according to drug instructions to obtain satisfactory therapeutic effect. However, some of off-label drug of use have certain rationality and necessity.

Investigation of radiation dose in CT scanning for adult patients in Ningxia / 中华放射医学与防护杂志

Objective@#To investigate the current status of CT radiation dose to adults in Ningxia, and provide basic data for developing the first diagnostic reference level of adults from CT scanning.@*Methods@#Stratified cluster sampling method was used to investigate the in-service status of CT scanners with various brands and different models in different grades of hospital in Ningxia. Interval sampling method was used to obtain everyday′s scanning parameters and radiation dose values from different types of scanning examinations in surveyed hostipitals. Basic information was collected include hospitals, CT scanner, scanning types and patients. CT scanning parameters, CTDIvol and DLP values were recorded, with effective dose values calculated. The data were statistically analyzed by examination types and comparation was made with the DRL values recommended by other countries.@*Results@#Finally, there were 45 medical institutions in this study, including 10 public tertiary A hospitals, 5 public tertiary B hospitals, 23 public secondary A hospitals, 5 private hospitals and 2 physical examination centers. 58 CT scanners from 6 manufacturers and 4 952 adult patients were investigated. The 75th percentile (P75) of CTDIvol, DLP, and E values of common scanning examinations were listed as follows: 65.67 mGy, 860.74 mGy·cm, and 1.64 mSv in skull scanning; 29.32 mGy, 490.00 mGy·cm, and 2.83 mSv in neck scanning; 36.92 mGy, 954.42 mGy·cm, and 4.87 mSv in neck enhanced scanning; 11.50 mGy, 382.06 mGy·cm , and 5.68 mSv in chest scanning; 45.80 mGy, 1 713.22 mGy·cm, and 25.01 mSv in chest enhanced scanning; 20.10 mGy, 506.59 mGy·cm, and 7.75 mSv in upper abdominal scanning; 50.07 mGy, 1 434.19 mGy·cm, and 21.94 mSv in upper abdominal enhanced scanning; 14.33 mGy, 670.78 mGy·cm, and 10.26 mSv in abdominal-pelvic scanning; 48.00 mGy, 2 294.00 mGy·cm, and 35.10 mSv in abdominal-pelvic enhanced scanning; 16.10 mGy, 471.58 mGy·cm, and 6.08 mSv in pelvic scanning; 31.04 mGy, 1 138.78 mGy·cm, and 14.69 mSv in pelvic enhanced scanning.@*Conclusions@#The CT scanning radiation doses to skull, neck, chest and pelvis in Ningxia are slightly lower than, or similar to, in other countries, but the abdominal scanning dose is significantly higher than that in other countries. It is necessary to optimize the abdominal CT scanning protocol.

Diagnostic Reference Levels for Adult Nuclear Medicine Imaging Established from the National Survey in Korea / 대한핵의학회잡지

PURPOSE: There is substantial need for optimizing radiation protection in nuclear medicine imaging studies. However, the diagnostic reference levels (DRLs) have not yet been established for nuclear medicine imaging studies in Korea.MATERIALS AND METHODS: The data of administered activity in 32 nuclear medicine imaging studies were collected from the Korean Society of Nuclear Medicine (KSNM) dose survey database from 2013 and 2014. Through the expert discussions and statistical analyses, the 75th quartile value (Q3) was suggested as the preliminary DRL values. Preliminary DRLs were subjected to approval process by the KSNM Board of Directors and KSNM Council, followed by clinical applications and performance rating by domestic institutes.RESULTS: DRLs were determined through 32 nuclear medicine imaging studies. The Q3 value was considered as appropriate selection as it was generally consistent with the most commonly administered activity. In the present study, the final version of initial DRL values for nuclear medicine imaging in Korean adults is described including various protocols of the brain and myocardial perfusion imaging.CONCLUSION: The first DRLs for nuclear medicine imaging in Korean adults were confirmed. The DRLs will enable optimized radiation protection in the field of nuclear medicine imaging in Korea.

User-Friendly Vendor-Specific Guideline for Pediatric Cardiothoracic Computed Tomography Provided by the Asian Society of Cardiovascular Imaging Congenital Heart Disease Study Group: Part 1. Imaging Techniques

Optimal performance of pediatric cardiothoracic computed tomography (CT) is technically challenging and may need different approaches for different types of CT scanners. To meet the technical demands and improve clinical standards, a practical, user-friendly, and vendor-specific guideline for pediatric cardiothoracic CT needs to be developed for children with congenital heart disease (CHD). In this article, we have attempted to describe such guideline based on the consensus of experts in the Asian Society of Cardiovascular Imaging CHD Study Group. This first part describes the imaging techniques of pediatric cardiothoracic CT, and it includes recommendations for patient preparation, scan techniques, radiation dose, intravenous injection protocol, post-processing, and vendor-specific protocols.

Is It Better to Enter a Volume CT Dose Index Value before or after Scan Range Adjustment for Radiation Dose Optimization of Pediatric Cardiothoracic CT with Tube Current Modulation?

OBJECTIVE: To determine whether the body size-adapted volume computed tomography (CT) dose index (CTD(vol)) in pediatric cardiothoracic CT with tube current modulation is better to be entered before or after scan range adjustment for radiation dose optimization. MATERIALS AND METHODS: In 83 patients, cardiothoracic CT with tube current modulation was performed with the body size-adapted CTDIvol entered after (group 1, n = 42) or before (group 2, n = 41) scan range adjustment. Patient-related, radiation dose, and image quality parameters were compared and correlated between the two groups. RESULTS: The CTDIvol after the CT scan in group 1 was significantly higher than that in group 2 (1.7 ± 0.1 mGy vs. 1.4 ± 0.3 mGy; p 0.05). In both groups, all patient-related parameters, except body density, showed positive correlations (r = 0.49–0.94; p 0.05) in group 2. CONCLUSION: In pediatric cardiothoracic CT with tube current modulation, the CTDIvol entered before scan range adjustment provides a significant dose reduction (18%) with comparable image quality compared with that entered after scan range adjustment.

Optimization Research on TCM Compound Prescription in Insomnia Treatment / 世界科学技术-中医药现代化

This study was aimed to screen out a safe and effective traditional Chinese medicine (TCM) compound prescription in insomnia treatment, through the method of uniform design and comprehensive scoring method. It provided candidate drugs to further research and development of TCM new drug. U7(76) uniform design was used to divide groups. The test was given on sleep time prolonging effect of mice injected with pentobarbital sodium. The subliminal dosage of pentobarbital hypnosis was tested on mice injected with pentobarbital sodium. The acute toxicity (LD50) was tested on mice. Comprehensive scoring method was applied to evaluate the effect to determine the optimum dose. The results showed the optimized prescription was composed of Radix Sophorae Flavescentis and Schisandra chinensis. The optimum ratio was 1:3. It was concluded that the uniform design was applied in the experimental design with 3 factors and 6 levels. Comprehensive scoring method was used to evaluate the combined effect. The optimized prescription that put benefit and risk into consideration was composed of Radix Sophorae Flavescentis and Schisandra chinensis. The best ratio was 1:3, which can be further developed.

Dose optimization of cyclophosphamide combined with cisplatin in treatment of tumor / 肿瘤研究与临床

Objective To investigate the optimum doses of combined chemotherapy with cyclophosphamide (CTX) and cisplatin (DDP).Methods 120 cases of ovarian cancer and malignant lymphoma were divided randomly into 6 groups.Drugs were administered to each group:CTX 500 mg/m2 + DDP 40 mg/m2,CTX 500 mg/m2 + DDP 50 mg/m2,CTX 500 mg/m2 + DDP 60 mg/m2,CTX 600 mg/m2 + DDP 40 mg/m2,CTX 600 mg/m2 + DDP 50 mg/m2,CTX 600 mg/m2 + DDP 60 mg/m2.Drugs were administered intravenously once a week for 2 consecutive weeks.Changes in the efficacy and adverse reaction were compared among the groups.Results There was no significant efficacy difference among the groups (P ＞ 0.05).Leukocyte inhibition rate (72.6 ％ and 79.3 ％,respectively) and damage to lymphocyte were maximal in the high-dose chemotherapy groups (CTX 500 mg/m2 + DDP 60 mg/m2,CTX 600 mg/m2 + DDP 60 mg/m2),and the levels of creatinine,blood urea nitrogen,alanine aminotransferase (ALT) in serum and aspartate aminotransferase (AST) were reduced significantly,whereas the hemogram was within normal range in the lowdose chemotherapy group (CTX500 mg/m2 + DDP 40 mg/m2),and the frequencies of damage to renal function and hepatic function were low.Conclusion The optimum dose of combined chemotherapy with cyclophosphamide and cisplatin was CTX 500 mg/m2 and DDP 40 mg/m2.

Modelado farmacocinético-farmacodinámico de fármacos antihipertensivos: su aplicación en la práctica clínica / Pharmacokinetic-Pharmacodynamic Modelling of Antihypertensive Drugs: Its Application to Clinical Practice

El conocimiento de las propiedades farmacocinéticas-farmacodinámicas (PK/PD) de los fármacos puede optimizar la terapia antihipertensiva. El modelado PK/PD en la investigación clínica podría contribuir en el desarrollo del fármaco y en la práctica clínica en varios aspectos, entre ellos la evaluación de eficacia y seguridad de los antihipertensivos, mayor información durante el proceso del desarrollo, identificación de factores de variabilidad de la respuesta farmacológica, y permitir además una identificación rápida de malos respondedores o no respondedores y ayudar a determinar requerimientos óptimos del fármaco y dosis en cada paciente hipertenso. Hay algunas limitaciones en el modelado PK/PD de los antihipertensivos en la práctica clínica, entre las que se incluyen el uso de modelos farmacodinámicos inadecuados y la incapacidad de estudiar dosis elevadas de antihipertensivos para determinar el rango farmacodinámico completo del efecto antihipertensivo. El propósito de esta revisión es describir el conocimiento actual del modelado PK/PD de los fármacos antihipertensivos en la investigación clínica y sus usos futuros.

Knowing the pharmacokinetic-pharmacodynamic properties (PK/PD) of drugs might optimize antihypertensive therapy. PK/PD modelling might not only contribute to develop the drug but might also help in clinical practice assessing the efficacy and safety of antihypertensive drugs, bringing more information during the developing process, identifying factors responsible for the variability in pharmacologic response, bad responders or non-responders, and determining the optimal requisites of the drug and doses in each patient with hypertension. There are some limitations in PK/ PD modelling of antihypertensive drugs in clinical practice, such as inadequate pharmacodynamic models and the inability to study high doses of antihypertensive drugs to determine the whole pharmacodynamic range of the antihypertensive effect. The aim of this review is to describe the current knowledge on PK/PD modelling of antihypertensive drugs in clinical research, and its further uses.

Optimization of Dose Distribution for High Dose Rate Intraluminal Therapy / 대한치료방사선과학회지

The use of high dose rate remote afterloading system for the treatment of intraluminal lesions necessitates the need for a more accurate of dose distributions around the high intensity brachytherapy sources, doses are often prescribed to a distance of few centimeters from the linear source, and in this range the dose distribution is very difficult to assess. Accurated and optimized dose calculation with stable numerical algorithms by PC level computer was required to treatment intraluminal lesions by high dose rate brachytherapy system. The exposure rate from sources was calculated with Sievert integral and dose rate in tissue was calculated with Meisberger equation. An algorithm for generating a treatment plan with optimized dose distribution was developed for high dose rate intraluminal radiotherapy. The treatment volume becomes the locus of the constrained target surface points that is the specified radial distance from the source dwelling positions. The treatment target volume may be alternately outlined on a x-ray film of the implant dummy sources. The routine used a linear programming formulism to compute which dwell time at each position to irradiate the constrained dose rate at the target surface points whiles minimizing the total volume integrated dose to the patient. The exposure rate and the dose distribution to be confirmed the result of calculation with algorithm were measured with film dosimetry, TLD and small size ion chambers.