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1.
J Craniofac Surg ; 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37938102

RESUMO

Contouring surgery is an operation that makes a smooth, oval-shaped face by removing protruding parts of the face. In particular, mandibuloplasty is a procedure that softens the shape of the mandible and is a popular procedure among Asians with a dominant mesocephalic profile. In this study, we tried to discuss the considerations before surgery by dividing the mandibular shape into morphologic aspects in the lateral and frontal views and anatomic considerations. In the lateral view, it is essential to consider the posterior ramal height and mandibular body length of each patient. These factors are closely related to the postoperative outcomes. Consideration of the mandibular plane angle is also essential. In the frontal view, the position of the gonial angle relative to the ramal body should be considered because the position of the gonial angle can affect the difficulty of operation. Anatomic considerations include antero-posterior ramal width, bucco-lingual width of mandibular body, amount of mouth opening, and location of inferior alveolar nerve. These are important factors that determine the difficulty of the operation. In this study, classification according to the shape and shape of the mandible was presented, and considerations for each classification were discussed. Cosmetic surgery is a socio-psychologically meaningful procedure that not only improves the esthetics but also improves the mental well-being of the patients. Therefore, it will be possible to provide better medical services to patients if clinicians are fully aware of the factors that can increase the difficulty of the operation and the factors that affect the surgical outcome.

2.
J Korean Neurosurg Soc ; 66(6): 716-725, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37670434

RESUMO

OBJECTIVE: Anterior cervical spine surgery (ACSS) is a common surgical procedure used to treat cervical spinal degenerative diseases. One of the complications associated with ACSS is prevertebral soft tissue swelling (PSTS), which can result in airway obstruction, dysphagia, and other adverse outcomes. This study aims to investigate the correlation between various cervical sagittal parameters and PSTS following single-level ACSS, as well as to identify independent risk factors for PSTS. METHODS: A retrospective study conducted at a single institution. The study population included all patients who underwent single-level ACSS between January 2014 and December 2022. Patients with a history of cervical spine surgery or trauma were excluded from the study. The presence and severity of PSTS was assessed by reviewing pre- and postoperative imaging studies. The potential risk factors for PSTS that were examined include patient age, sex, body mass index, tobacco use, comorbidities, serum albumin levels, operative time, implant type, implanted level, and various cervical spine sagittal parameters. Multivariate linear regression analysis was performed to identify the independent risk factors for PSTS. RESULTS: A total of 62 consecutive patients who underwent single-level ACSS over a 8-year period at a single institution were enrolled in this study. Only preoperative segmental angle showed positive correlation with PSTS among various cervical spine sagittal parameters (r=0.36, p=0.005). Artificial disc replacement showed a negative correlation with PSTS (ß=-0.38, p=0.002), whereas the use of demineralized bone matrix (DBM) had a positive impact on PSTS (ß=0.33, p=0.009). We found that male sex, lower preoperative serum albumin, and implantation of upper cervical level (above C5) were independent predictors for PSTS after single-level ACSS (ß=1.21; 95% confidence interval [CI], 0.27 to 2.15; p=0.012; ß=-1.63; 95% CI, -2.91 to -0.34; p=0.014; ß=1.44; 95% CI, 0.38 to 2.49; p=0.008, respectively). CONCLUSION: Our study identified male sex, lower preoperative serum albumin levels, and upper cervical level involvement as independent risk factors for PSTS after single-level ACSS. These findings can help clinicians monitor high-risk patients and take preventive measures to reduce complications. Further research with larger sample sizes and prospective designs is needed to validate these findings.

3.
Physiol Meas ; 44(5)2023 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-36638544

RESUMO

Objective.Recently, many electrocardiogram (ECG) classification algorithms using deep learning have been proposed. Because the ECG characteristics vary across datasets owing to variations in factors such as recorded hospitals and the race of participants, the model needs to have a consistently high generalization performance across datasets. In this study, as part of the PhysioNet/Computing in Cardiology Challenge (PhysioNet Challenge) 2021, we present a model to classify cardiac abnormalities from the 12- and the reduced-lead ECGs.Approach.To improve the generalization performance of our earlier proposed model, we adopted a practical suite of techniques, i.e. constant-weighted cross-entropy loss, additional features, mixup augmentation, squeeze/excitation block, and OneCycle learning rate scheduler. We evaluated its generalization performance using the leave-one-dataset-out cross-validation setting. Furthermore, we demonstrate that the knowledge distillation from the 12-lead and large-teacher models improved the performance of the reduced-lead and small-student models.Main results.With the proposed model, our DSAIL SNU team has received Challenge scores of 0.55, 0.58, 0.58, 0.57, and 0.57 (ranked 2nd, 1st, 1st, 2nd, and 2nd of 39 teams) for the 12-, 6-, 4-, 3-, and 2-lead versions of the hidden test set, respectively.Significance.The proposed model achieved a higher generalization performance over six different hidden test datasets than the one we submitted to the PhysioNet Challenge 2020.


Assuntos
Fibrilação Atrial , Humanos , Algoritmos , Eletrocardiografia/métodos , Entropia
4.
Curr Psychol ; 42(12): 10186-10199, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34566389

RESUMO

Because military special forces carry out dangerous missions, they are much more exposed to adversities and traumatic events compared to other occupational groups. According to Posttraumatic Growth theory, individuals tend to obtain positive growth through adversities. Moreover, a framework of Psychosocial Gains from Adversity argues not only individual changes but also social changes in the group to which the individual belongs are induced. Therefore, the present study aimed to explore the adverse experiences of special forces operatives and delineate the positive shift at an individual and social level via Consensual Qualitative Research (CQR). Eight individuals serving in special forces at the Korean Army, Navy and Air Force were interviewed using a semi-structured protocol. Four domains including 10 categories and 34 subcategories were identified: (a) Adverse experiences; (b) Personal change; (c) Social change; and (d) Attributes related to adverse experience. The findings and clinical implications are discussed in light of growth over facing adversities and interaction between personal and social factors.

5.
Nat Mater ; 21(11): 1298-1305, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36050382

RESUMO

Understanding and mitigating filament formation, short-circuit and solid electrolyte fracture is necessary for advanced all-solid-state batteries. Here, we employ a coupled far-field high-energy diffraction microscopy and tomography approach for assessing the chemo-mechanical behaviour for dense, polycrystalline garnet (Li7La3Zr2O12) solid electrolytes with grain-level resolution. In situ monitoring of grain-level stress responses reveals that the failure mechanism is stochastic and affected by local microstructural heterogeneity. Coupling high-energy X-ray diffraction and far-field high-energy diffraction microscopy measurements reveals the presence of phase heterogeneity that can alter local chemo-mechanics within the bulk solid electrolyte. These local regions are proposed to be regions with the presence of a cubic polymorph of LLZO, potentially arising from local dopant concentration variation. The coupled tomography and FF-HEDM experiments are combined with transport and mechanics modelling to illustrate the degradation of polycrystalline garnet solid electrolytes. The results showcase the pathways for processing high-performing solid-state batteries.


Assuntos
Fontes de Energia Elétrica , Eletrólitos , Eletrólitos/química , Difração de Raios X , Microscopia , Tomografia Computadorizada por Raios X
6.
Proc Natl Acad Sci U S A ; 119(28): e2202044119, 2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35867742

RESUMO

Liquid polymorphism is an intriguing phenomenon that has been found in a few single-component systems, the most famous being water. By supercooling liquid Te to more than 130 K below its melting point and performing simultaneous small-angle and wide-angle X-ray scattering measurements, we observe clear maxima in its thermodynamic response functions around 615 K, suggesting the possible existence of liquid polymorphism. A close look at the underlying structural evolution shows the development of intermediate-range order upon cooling, most strongly around the thermodynamic maxima, which we attribute to bond-orientational ordering. The striking similarities between our results and those of water, despite the lack of hydrogen-bonding and tetrahedrality in Te, indicate that water-like anomalies may be a general phenomenon among liquid systems with competing bond- and density-ordering.

7.
Medicina (Kaunas) ; 58(5)2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35630014

RESUMO

The purpose of this case report is to introduce a novel guided bone regeneration (GBR) technique that utilized bone harvested from previously grafted maxillary sinus with deproteinized bovine bone mineral (DBBM) 16 years ago. The patient is a 63-year-old male with hopeless maxillary right molars due to severe bone loss. Two months after the extraction, two bone blocks were harvested with a trephine drill from the lateral wall. One was used for histologic analysis and the other was crushed into particulate forms, which was used for a GBR procedure around an implant at the time of implant placement. The grafted site was then covered with a resorbable collagen membrane. The histological specimen showed newly-formed bone containing residual DBBM particles. The DBBM in the harvested bone was mostly resorbed; DBBM particles comprised only 3.6% of the total bone volume. The final prosthesis was delivered six months post-operatively. No change in crestal bone around the implant was observed throughout the 2 year follow-up period. Within the limitation of the present case report, previously grafted sinus can be a good donor site for further harvesting for a successful GBR procedure.


Assuntos
Substitutos Ósseos , Animais , Bovinos , Colágeno/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Próteses e Implantes
8.
J Med Imaging (Bellingham) ; 9(3): 031504, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35127969

RESUMO

Purpose: Tomography using diffracted x-rays produces reconstructions mapping quantities such as crystal lattice parameter(s), crystallite size, and crystallographic texture, information quite different from that obtained with absorption or phase contrast. Diffraction tomography is used to map an entire blue shark centrum with its double cone structure (corpora calcerea) and intermedialia (four wedges). Approach: Energy dispersive diffraction (EDD) and polychromatic synchrotron x-radiation at 6-BM-B, the Advanced Photon Source, were used. Different, properly oriented Bragg planes diffract different x-ray energies; these intensities are measured by one of ten energy-sensitive detectors. A pencil beam defines the irradiated volume, and a collimator before each energy-sensitive detector selects which portion of the irradiated column is sampled at any one time. Translating the specimen along X , Y , and Z axes produces a 3D map. Results: We report 3D maps of the integrated intensity of several bioapatite reflections from the mineralized cartilage centrum of a blue shark. The c axis reflection's integrated intensities and those of a reflection with no c axis component reveal that the cone wall's bioapatite is oriented with its c axes lateral, i.e., perpendicular to the backbone's axis, and that the wedges' bioapatite is oriented with its c axes axial. Absorption microcomputed tomography (laboratory and synchrotron) and x-ray excited x-ray fluorescence maps provide higher resolution views. Conclusion: The bioapatite in the cone walls and wedges is oriented to resist lateral and axial deflections, respectively. Mineralized tissue samples can be mapped in 3D with EDD tomography and subsequently studied by destructive methods.

9.
IUCrJ ; 9(Pt 1): 104-113, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35059215

RESUMO

X-ray diffraction based microscopy techniques such as high-energy diffraction microscopy (HEDM) rely on knowledge of the position of diffraction peaks with high precision. These positions are typically computed by fitting the observed intensities in detector data to a theoretical peak shape such as pseudo-Voigt. As experiments become more complex and detector technologies evolve, the computational cost of such peak-shape fitting becomes the biggest hurdle to the rapid analysis required for real-time feedback in experiments. To this end, we propose BraggNN, a deep-learning based method that can determine peak positions much more rapidly than conventional pseudo-Voigt peak fitting. When applied to a test dataset, peak center-of-mass positions obtained from BraggNN deviate less than 0.29 and 0.57 pixels for 75 and 95% of the peaks, respectively, from positions obtained using conventional pseudo-Voigt fitting (Euclidean distance). When applied to a real experimental dataset and using grain positions from near-field HEDM reconstruction as ground-truth, grain positions using BraggNN result in 15% smaller errors compared with those calculated using pseudo-Voigt. Recent advances in deep-learning method implementations and special-purpose model inference accelerators allow BraggNN to deliver enormous performance improvements relative to the conventional method, running, for example, more than 200 times faster on a consumer-class GPU card with out-of-the-box software.

10.
Comput Methods Programs Biomed ; 214: 106521, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34844765

RESUMO

BACKGROUND AND OBJECTIVES: Most deep-learning-related methodologies for electrocardiogram (ECG) classification are focused on finding an optimal deep-learning architecture to improve classification performance. However, in this study, we proposed a methodology for fusion of various single-lead ECG data as training data in the single-lead ECG classification problem. METHODS: We used a squeeze-and-excitation residual network (SE-ResNet) with 152 layers as the baseline model. We compared the performance of a 152-layer SE-ResNet trained on ECG signals from various leads of a standard 12-lead ECG system to that of a 152-layer SE-ResNet trained on only single-lead ECG data with the same lead information as the test set. The experiments were performed using five different types of rhythm-type single-lead ECG data obtained from Konkuk University Hospital in South Korea. RESULTS: Experiment results based on the combination from the relationship experiments of the leads showed that lead -aVR or II revealed the best classification performance. In case of -aVR, this model achieved a high F1 score for normal (98.7%), AF (98.2%), APC (95.1%), and VPC (97.4%), indicating its potential for practical use in the medical field. CONCLUSION: We concluded that the 152-layer SE-ResNet trained by fusion of single-lead ECGs had better classification performance than the 152-layer SE-ResNet trained on only single-lead ECG data, regardless of the single-lead ECG signal type. We also found that the best performance directions for single-lead ECG classification are Lead -aVR and II.


Assuntos
Algoritmos , Redes Neurais de Computação , Eletrocardiografia , Humanos , República da Coreia
11.
Clin Exp Reprod Med ; 47(4): 284-292, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33227188

RESUMO

OBJECTIVE: This study investigated whether adding outer-well medium to inhibit osmotic changes in culture media in a dry-type incubator improved the clinical outcomes of in vitro fertilization-embryo transfer (IVF-ET) cycles. METHODS: In culture dishes, the osmotic changes in media (20 µL)-covered oil with or without outer-well medium (humid or dry culture conditions, respectively) were compared after 3 days of incubation in a dry-type incubator. One-step (Origio) and G1/G2 (Vitrolife) media were used. RESULTS: The osmotic changes in the dry culture condition (308 mOsm) were higher than in the humid culture conditions (285-290 mOsm) after 3 days of incubation. In day 3 IVF-ET cycles, although the pregnancy rate did not significantly differ between the dry (46.2%) and humid culture (52.2%) groups, the rates of abortion and ongoing pregnancy were significantly better in the humid culture group (2.3% and 50.2%, respectively) than in the dry culture group (8.3% and 37.8%, respectively, p<0.05). In day 5 IVF-ET cycles, the abortion rate was significantly lower in the humid culture group (2.2%) than in the dry culture group (25.0%, p<0.01), but no statistically significant difference was observed in the rates of clinical and ongoing pregnancy between the dry (50.0% and 25.0%, respectively) and humid culture groups (59.5% and 57.3%, respectively) because of the small number of cycles. CONCLUSION: Hyperosmotic changes in media occurred in a dry-type incubator by evaporation, although the medium was covered with oil. These osmotic changes were efficiently inhibited by supplementation of outer-well medium, which resulted in improved pregnancy outcomes.

12.
J Dent Anesth Pain Med ; 20(4): 251-259, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32934991

RESUMO

Oral and maxillofacial infection is a common complication in patients undergoing chemotherapy. The treatment of oral diseases in such patients differs from that administered to healthy patients. This paper reports a case of acute osteomyelitis of odontogenic origin following a recent chemotherapy session. The patient's condition was life-threatening because of neutropenic fever and sepsis that developed during the inpatient supportive care. However, the patient showed prompt recovery within 40 days following the use of appropriate antibiotics and routine dressing, without the requirement for surgical treatment, except tooth extraction. As seen in this case, patients undergoing chemotherapy are more susceptible to rapid progression of infections in the oral and maxillofacial areas. Therefore, accurate diagnosis through prompt clinical and radiological examination, identification of the extent of infection, and assessment of the patient's immune system are crucial for favorable outcomes. It is also necessary to eliminate the source of infection through appropriate administration of antibiotics. In particular, a broad-spectrum antibiotic with anti-pneumococcal activity is essential. Proper antibiotic administration and wound dressing are essential for infection control. Furthermore, close consultation with a hemato-oncologist is necessary for effective infection management based on the professional evaluation of patients' immune mechanisms.

13.
Rev Sci Instrum ; 89(6): 063701, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29960547

RESUMO

We demonstrate a hydrogen gas chamber suitable for lattice strain measurements and capturing radiographs of a steel specimen under a mechanical load using high energy synchrotron x-rays. The chamber is suitable for static and cyclic mechanical loading. Experiments were conducted at the 1-ID-E end station of the Advanced Photon Source, Argonne National Laboratory. Diffraction patterns show a high signal-to-noise ratio suitable for lattice strain measurements for the specimen and with minimal scattering and overlap from the gas chamber manufactured from aluminum. In situ radiographs of a specimen in the hydrogen chamber show the ability to track a growing crack and to map the lattice strain around the crack with high spatial and strain resolution.

14.
Rev Sci Instrum ; 88(1): 015111, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28147640

RESUMO

We present an in situ Radiated Materials (iRadMat) experimental module designed to interface with a servo-hydraulic load frame for X-ray measurements at beamline 1-ID at the Advanced Photon Source. This new capability allows in situ studies of radioactive specimens subject to thermo-mechanical loading using a suite of high-energy X-ray scattering and imaging techniques. The iRadMat is a radiation-shielded vacuum heating system with the sample rotation-under-load capability. We describe the design features and performances of the iRadMat and present a dataset from a 300 °C uniaxial tensile test of a neutron-irradiated pure Fe specimen to demonstrate its capabilities.

15.
Phys Rev E ; 96(4-2): 049904, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29347545

RESUMO

This corrects the article DOI: 10.1103/PhysRevE.94.022310.

16.
Phys Rev E ; 94(2-1): 022310, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27627320

RESUMO

A concept of bypass rewiring is introduced, and random bypass rewiring is analytically and numerically investigated with simulations. Our results show that bypass rewiring makes networks robust against removal of nodes including random failures and attacks. In particular, random bypass rewiring connects all nodes except the removed nodes on an even degree infinite network and makes the percolation threshold 0 for arbitrary occupation probabilities. In our example, the even degree network is more robust than the original network with random bypass rewiring, while the original network is more robust than the even degree networks without random bypass. We propose a greedy bypass rewiring algorithm which guarantees the maximum size of the largest component at each step, assuming which node will be removed next is unknown. The simulation result shows that the greedy bypass rewiring algorithm improves the robustness of the autonomous system of the Internet under attacks more than random bypass rewiring.

17.
J Mech Behav Biomed Mater ; 57: 128-38, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26710258

RESUMO

Water, an important constituent in bone, resides in different compartments in bone matrix and may impose significant effects on its bulk mechanical properties. However, a clear understanding of the mechanistic role of water in toughening bone is yet to emerge. To address this issue, this study used a progressive loading protocol, coupled with measurements of in situ mineral and collagen fibril deformations using synchrotron X-ray diffraction techniques. Using this unique approach, the contribution of water to the ultrastructural behavior of bone was examined by testing bone specimens in different loading modes (tension and compression) and hydration states (wet and dehydrated). The results indicated that the effect of water on the mechanical behavior of mineral and collagen phases at the ultrastructural level was loading-mode dependent and correlated with the bulk behavior of bone. Tensile loading elicited a transitional drop followed by an increase in load bearing by the mineral phase at the ultrastructural level, which was correlated with a strain hardening behavior of bone at the bulk level. Compression loading caused a continuous loss of load bearing by the mineral phase, which was reflected at the bulk level as a strain softening behavior. In addition, viscous strain relaxation and pre-strain reduction were observed in the mineral phase in the presence of water. Taken together, the results of this study suggest that water dictates the bulk behavior of bone by altering the interaction between mineral crystals and their surrounding matrix.


Assuntos
Força Compressiva , Fêmur/metabolismo , Nanotecnologia , Estresse Mecânico , Água/metabolismo , Fenômenos Biomecânicos , Colágeno/química , Colágeno/metabolismo , Elasticidade , Humanos , Teste de Materiais , Minerais/química , Minerais/metabolismo , Viscosidade
18.
Materials (Basel) ; 9(1)2016 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-28787819

RESUMO

In this study, an MA957 oxide dispersion-strengthened (ODS) alloy was irradiated with high-energy ions in the Argonne Tandem Linac Accelerator System. Fe ions at an energy of 84 MeV bombarded MA957 tensile specimens, creating a damage region ~7.5 µm in depth; the peak damage (~40 dpa) was estimated to be at ~7 µm from the surface. Following the irradiation, in-situ high-energy X-ray diffraction measurements were performed at the Advanced Photon Source in order to study the dynamic deformation behavior of the specimens after ion irradiation damage. In-situ X-ray measurements taken during tensile testing of the ion-irradiated MA957 revealed a difference in loading behavior between the irradiated and un-irradiated regions of the specimen. At equivalent applied stresses, lower lattice strains were found in the radiation-damaged region than those in the un-irradiated region. This might be associated with a higher level of Type II stresses as a result of radiation hardening. The study has demonstrated the feasibility of combining high-energy ion radiation and high-energy synchrotron X-ray diffraction to study materials' radiation damage in a dynamic manner.

19.
Drug Des Devel Ther ; 9: 695-706, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25678774

RESUMO

The aim of present study was to design oxycodone once-a-day controlled-release (CR) tablets and to perform in vitro/in vivo characterizations. Release profiles to achieve desired plasma concentration versus time curves were established by using simulation software and reported pharmacokinetic parameters of the drug. Hydroxypropyl methylcellulose (HPMC) 100,000 mPa·s was used as a release modifier because the polymer was found to be resistant to changes in conditions of the release study, including rotation speed of paddle and ion strength. The burst release of the drug from the CR tablets could be suppressed by applying an additional HPMC layer as a physical barrier. Finally, the oxycodone once-a-day tablet was comprised of two layers, an inert HPMC layer and a CR layer containing drug and HPMC. Commercial products, either 10 mg bis in die (bid [twice a day]) or once-a-day CR tablets (20 mg) were administered to healthy volunteers, and calculated pharmacokinetic parameters indicated bioequivalence of the two different treatments. The findings of the present study emphasize the potential of oxycodone once-a-day CR tablets for improved patient compliance, safety, and efficacy, which could help researchers to develop new CR dosage forms of oxycodone.


Assuntos
Analgésicos Opioides/administração & dosagem , Oxicodona/administração & dosagem , Administração Oral , Analgésicos Opioides/sangue , Analgésicos Opioides/química , Analgésicos Opioides/farmacocinética , Química Farmacêutica , Estudos Cross-Over , Preparações de Ação Retardada , Esquema de Medicação , Voluntários Saudáveis , Humanos , Derivados da Hipromelose/química , Masculino , Oxicodona/sangue , Oxicodona/química , Oxicodona/farmacocinética , Solubilidade , Comprimidos , Tecnologia Farmacêutica/métodos , Equivalência Terapêutica
20.
Arch Pharm Res ; 38(1): 73-80, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24627339

RESUMO

This study was to evaluate the pharmacokinetics and bioequivalence of two tacrolimus formulations which had different in vitro drug release profiles. Dynamic solubility, in vitro dissolution profiles of the two formulations, and their influence on pharmacokinetics were examined. The male volunteers were randomly assigned to receive a single 1-mg capsule of the test or reference formulation and pharmacokinetic parameters were determined using a noncompartmental method. The two formulations released >85 % of tacrolimus in water within 30 min, which passed the criterion of evaluating the test formulation. However, the test formulation produced a faster initial release rate and plateaued in about 15 min, while the reference showed almost zero order initial release profiles. The AUC0-∞ values were 145.92 (reference) and 140.49 ng h/mL (test). The mean Cmax was 15.70 (reference) and 16.08 ng/mL (test) with Tmax values of 1.63 and 1.60 h, respectively. The t1/2 for the reference and test formulations was 29.12 and 27.85 h, respectively. Relative bioavailability was calculated to be 96.28 %. The point estimates for the mean ratio of the test to reference for the AUC0-t and Cmax were 0.969 and 1.026, respectively, satisfying the criterion for bioequivalence. The results suggest that the test formulation is pharmacokinetically equivalent to the reference in terms of both rate and extent of absorption. Even though the in vitro dissolution profiles of the formulations might not be equivalent, the pharmacokinetics indicated bioequivalence. Therefore, when developing poorly soluble drugs, it might be beneficial to pay attention to the dynamic solubility as well as dissolution profiles.


Assuntos
Tacrolimo/química , Tacrolimo/farmacocinética , Adulto , Disponibilidade Biológica , Química Farmacêutica , Estudos Cross-Over , Composição de Medicamentos , Humanos , Masculino , Pessoa de Meia-Idade , Solubilidade , Tacrolimo/sangue , Equivalência Terapêutica , Adulto Jovem
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