Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Computational prediction”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,009 records · Page 56Linked to original sources
PubMedDate not supplied

Early nonenhanced abdominal computed tomography can predict mortality in severe acute pancreatitis.

We wondered whether nonenhanced computed tomography (CT) within 48 hours of admission could identify individuals at risk for higher mortality from acute pancreatitis. Data from the international phase III study of the platelet-activating factor-inhibitor Lexipafant was used to analyze noncontrast CT versus acute pancreatitis mortality. Nonenhanced CT examinations of the abdomen from the trial were classified by disease severity (Balthazar grades A-E) and then correlated with patient survival. Among the 477 individuals who underwent CT within 48 hours of admission and 220 individuals who did so over the subsequent 6 days, higher CT grades were associated with increased mortality. Each unit increase in Balthazar grade during the initial 48 hours was associated with an estimated increase in the risk of mortality of 33%, and this trend increased to 50% if pancreatic enlargement and peripancreatic stranding (grades B and C) were combined (P<0.05). CT grade correlated minimally with Ranson, Glasgow, or APACHE II score during the initial 48 hours; however, this correlation improved over 3-8 days. Early nonenhanced abdominal CT in patients with acute pancreatitis is a valuable prognostic indicator of mortality in acute pancreatitis, even among patients without clinical features of severe acute pancreatitis.

APACHE↗
PubMed2000

Usefulness of topography of coronary calcium by electron-beam computed tomography in predicting the natural history of coronary atherosclerosis.

Electron-beam computed tomography (EBCT) allows for accurate noninvasive detection and quantification of coronary calcium that is representative of underlying atherosclerotic disease. The present study quantitatively analyzes the topography and establishes the natural history of coronary calcium in patients with variable degrees of coronary atherosclerosis. EBCT was performed in 330 consecutive patients aged 56 +/- 12 years (70% men) with recent (<3 months) onset of signs or symptoms of coronary artery disease (CAD) or who were evaluated because of a presumed high risk. Total calcium scores, computed by the Agatston method, were positive in 269 patients (82%) (mean age 58 +/- 11 years, 73% men). These patients were classified into 4 groups, with total calcium scores ranging between 1 and 30, >30 and 100, >100 and 400, and >400, respectively. The presence and amount of calcium was additionally assessed in 10 major segments of the coronary arterial tree, including the major coronary arteries. Of the 72 patients with calcium of only 1 of the major coronary arteries, the left anterior descending coronary artery was involved in 39 patients (54%) and the right coronary artery in 18 patients (25%). Left main stem calcium was observed in only 10 of 139 patients (7%) with 1- or 2-vessel calcium and in 17 of 77 patients (23%) with 3-vessel calcium. Calcium was consistent most frequently in the proximal left anterior descending coronary artery, followed by the proximal left circumflex and right coronary artery segments. A significant decrease of frequency and amount of calcium from the proximal to distal segments was observed in the left coronary system but not in the right coronary artery, where the distribution was more even. With increasing total calcium scores, segmental scores in the more distal segments were enhanced, but the increase was most pronounced in the proximal segments and particularly in the proximal left anterior descending coronary artery. EBCT-derived coronary calcium shows an axial distribution that appears comparable to that of atherosclerotic lesions observed in pathologic and angiographic studies, highlighting the potential role of EBCT for studying the natural history of CAD.

Aged↗
PubMedDate not supplied

Infectious pulmonary nodules in immunocompromised patients: usefulness of computed tomography in predicting their etiology.

PURPOSE: To review the high-resolution computed tomography (CT) findings in immunocompromised patients who had nodular opacities and a proven diagnosis to determine whether the various infectious pulmonary nodules have distinguishing features on CT. MATERIALS AND METHODS: The high-resolution CT scans obtained in 78 immunocompromised patients with solitary or multiple nodular opacities of proven infectious etiology were reviewed retrospectively by 2 independent thoracic radiologists. Patients whose predominant abnormality consisted of branching linear or nodular opacities (tree-in-bud pattern) characteristic of infectious bronchiolitis and endobronchial spread of tuberculosis were excluded. The CT scans were assessed for the presence, appearance, size, and distribution of parenchymal nodules. Relations between findings at CT and the different infectious etiologies of nodules were assessed with regression analysis. Agreement between the 2 observers was assessed using the kappa statistic. RESULTS: The infectious causes included mycobacteria (n = 24), fungi (n = 22), bacteria (n = 20), and viruses (n = 12). Multivariate analysis demonstrated that a diameter <10 mm was the only independent predictor of etiology (P < 0.0001) and that patients whose nodules all measured less than 10 mm in diameter were most likely to have a viral infection. Nodules limited in size to less than 10 mm in diameter were seen in 83% of viral infections compared with 5% of bacterial infections (odds ratio [OR] = 95.0; 95% confidence interval (CI): 6.08-4,321.5, P < 0.0001), 0% of mycobacterial infections (OR = 91.7; 95% CI: 7.21-4,090.22, P < 0.0001), and 14% of fungal infections (OR = 31.67; 95% CI: 3.56-375.09, P = 0.0003). CONCLUSION: Although some overlap exists, nodule size is helpful in the differential diagnosis of infectious causes of nodules in immunocompromised patients. Patients whose nodules are all less than 10 mm in diameter are most likely to have a viral infection.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Utility of high resolution computed tomography in predicting bronchiolitis obliterans syndrome following lung transplantation: preliminary findings.

This study was undertaken to evaluate the efficacy of high resolution computed tomography (HRCT) in predicting the development of bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. Fifty lung transplant patients who were clinically stable and without evidence of BOS were evaluated for the presence of four HRCT features reported to be associated with bronchiolitis obliterans: mosaic attenuation on inspiratory CT (mosaic perfusion), mosaic attenuation on expiratory CT (air trapping), bronchiectasis, and tree-in-bud opacities. CT exams were part of an annual surveillance process with the hope of predicting subsequent development of BOS. Diagnosis of BOS was made in 9 of 50 patients as indicated by a fall in FEV1 of greater than 20% of a stable baseline. None of the radiographic features associated with clinically established BOS were both sensitive and specific in the prediction of BOS. Air trapping demonstrated moderate sensitivity (56%, 5/9) and moderate specificity (76%, 35/46) for prediction of BOS in the year following the CT exam. Bronchiectasis, the most reliable indicator of the presence of BOS was a poor predictor of subsequent BOS with an 11% (1/9) sensitivity but had high specificity (96%, 44/46). No high resolution CT features accurately predicted the development of BOS.

Adult↗
PubMedDate not supplied

Accuracy of serum gentamicin concentration predictions generated by a personal-computer software system.

Predictions of serum gentamicin concentration and half-life, using a personal-computer software system (SIMKIN [simulated kinetics]), were compared for accuracy as increasing amounts of patient-specific data were supplied to the computer. Data for a two-year period were collected for patients of a hospital's pharmacokinetic consultation service; the study group included adults who had at least one serum concentration for which time of last gentamicin dose was recorded. Input variables were age, weight, height, sex, serum creatinine concentration, concomitant drugs and diseases, gentamicin dosage, time of infusion, dosing interval, number of doses on each regimen, and time and reported value of all serum gentamicin concentrations. Individualized dosing regimens were calculated on the basis of literature estimates, and half-life and serum concentrations were then estimated for these regimens and compared with actual values. One or two measured serum concentrations were then added to the input data. The computer-estimated half-lives (obtained from single-point or two-point analysis in different dosage intervals) were compared with the half-lives determined from actual serum concentration data. Gentamicin serum concentrations were similarly compared. The computer's ability to predict subsequent serum concentrations improved in sequence for literature-averaged prediction and single-point and multipoint analysis. Accuracy of predicting whether peak concentrations were therapeutic or subtherapeutic and whether trough concentrations were toxic also improved as more patient-specific data were input. SIMKIN appropriately evaluated demographic and laboratory data and adequately predicted gentamicin half-lives and serum concentrations.

Adolescent↗
PubMed1988

A computer protocol to predict myocardial infarction in emergency department patients with chest pain.

To achieve more appropriate triage to the coronary care unit of patients presenting with acute chest pain, we used clinical data on 1379 patients at two hospitals to construct a simple computer protocol to predict the presence of myocardial infarction. When we tested this protocol prospectively in 4770 patients at two university hospitals and four community hospitals, the computer-derived protocol had a significantly higher specificity (74 vs. 71 percent) in predicting the absence of infarction than physicians deciding whether to admit patients to the coronary care unit, and it had a similar sensitivity in detecting the presence of infarction (88.0 vs. 87.8 percent). Decisions based solely on the computer protocol would have reduced the admission of patients without infarction to the coronary care unit by 11.5 percent without adversely affecting the admission of patients in whom emergent complications developed that required intensive care. Although this protocol should not be used to override careful clinical judgment in individual cases, the computer protocol for the most part yields accurate estimates of the probability of myocardial infarction. Decisions about admission to the coronary care unit based on the protocol would have been as effective as those actually made by the unaided physicians who cared for the patients, and less costly. Whether physicians who are aided by the protocol perform better than unaided physicians cannot be determined without further study.

Angina Pectoris↗
PubMed1993

Can pretreatment computed tomography findings predict local control in T3 squamous cell carcinoma of the glottic larynx treated with radiotherapy alone?

PURPOSE: To determine if pretreatment computed tomography findings can predict local control in T3 squamous cell carcinoma of the glottic larynx treated with radiotherapy alone. METHODS AND MATERIALS: Twenty-nine patients with previously untreated T3 squamous cell carcinoma of the glottic larynx were treated for cure with radiotherapy alone; all had a minimum 2-year follow-up. High-quality pretreatment computed tomography scans were retrospectively reviewed by a single head and neck radiologist for tumor involvement of various anatomic subsites within the larynx, and total tumor volumes were calculated for 18 of the most recent patients using a computer digitizer. A tumor score was calculated and assigned to each primary lesion depending on the extent of laryngeal spread. RESULTS: A significant decrease in the local control rate was observed for cancers involving the face of the arytenoid (11 of 20 [55%] vs. 9 of 9 [100%]; p = .02), or the paraglottic space at the false vocal cord level (7 of 16 [44%] vs. 13 of 13 [100%]; p not equal to < .01). Tumors assigned a high tumor score (6, 7, or 8) had a significantly decreased rate of local control with radiation therapy when compared with tumors assigned a low tumor score (< or = 5): 1 of 7 (14%) vs. 19 of 22 (86%) (p = .01). Total tumor volume also significantly correlated with the rate of tumor control. For tumors measuring 3.5 cm3 or less, local control was achieved in 11 of 12 patients (92%), whereas for tumors greater than 3.5 cm3, local control was achieved in 2 of 6 patients (33%) (p = .02). CONCLUSION: Pretreatment computed tomography scans can contribute significantly to the treatment decision for patients with T3 glottic carcinoma and can define a subset of patients with an excellent chance of being cured with preservation of a functional larynx after treatment with radiotherapy alone.

Adult↗
PubMedDate not supplied

The value of computed tomography for predicting empyema-associated malignancy.

OBJECTIVE: To determine the value of computed tomography (CT) scanning in detecting associated malignancy in patients with chronic empyema. METHODS: Two radiologists retrospectively reviewed CT scans of 112 consecutive patients with chronic empyema and arrived at a consensus about the findings. Among these patients, 6 were confirmed by pathology evaluation to have empyema-associated malignancy (EAM), including 4 lymphomas. The CT scans were evaluated for the presence of the following findings: a mass in the empyema sac; mass involvement of the extrapleural fat, chest wall, rib, and lung; bulging of the empyema sac; nodular pleural thickening; empyema involvement of the mediastinal pleura; presence of lung nodules (>1 cm); and mediastinal lymph node enlargement. The association between the CT findings and the EAM was analyzed with the Fisher exact test. A multiple logistic regression analysis was used to determine the predictive variables for EAM. Sensitivity, specificity, and positive predictive value were calculated for each finding. RESULTS: All CT findings, except rib involvement and bulging of empyema sac, were significantly associated with EAM (P<0.05). The finding of the presence of a mass, extrapleural fat, and mediastinal involvement showed relatively high sensitivity (100%, 67%, 67%, respectively) and specificity (81%, 87%, 91%, respectively). A bulging of the empyema sac and nodular pleural thickening showed 100% sensitivity, but low specificity (39% and 44%, respectively). Findings from the multiple logistic regression analysis revealed that the presence of a mass and empyema of the mediastinal pleura were significant variables associated with EAM (P<0.05). CONCLUSIONS: Although many CT findings are associated with EAM, most showed either low positive predictive value or low sensitivity. A variety of CT findings should be considered when evaluating CT image-based detection of EAM.

Adolescent↗
PubMed2003

Use of computed tomography to predict the outcome of a noninvasive intranasal infusion in dogs with nasal aspergillosis.

Computed tomography (CT) was performed on 36 dogs with nasal aspergillosis to assess whether this imaging technique can be used to predict the success of a noninvasive intranasal infusion of enilconazole. A CT score based on the severity of the disease was given to each dog, prior to treatment, by dividing the nasal cavities and frontal sinuses into 8 anatomical regions. After therapy, the dogs were classified into 2 response groups (success group: dogs cured after 1 treatment; failure group: dogs needing more than 1 treatment or with treatment failure). No significant relationship on the logistic scale was found between the CT score and the response to treatment. High sensitivity (treatment failures correctly predicted) and specificity (treatment successes correctly predicted) could not be obtained at the same time, whatever the cut-off value chosen. The results of this study suggest that CT cannot predict the therapeutic success of nasal aspergillosis in dogs treated with a 1-hour infusion of enilconazole. However, dogs with a low score seem to be good candidates to respond after 1 treatment.

Administration, Intranasal↗
PubMed1992

A computer model to predict the effects of level of nutrition on composition of empty body gain in beef cattle: II. Evaluation of the model.

A computer model developed to predict composition of empty body gain of beef cattle fed at different levels of nutrition was evaluated with data from one unpublished and seven published experiments. These experiments used several breeds of beef cattle growing at rates that varied from negative to fast and various combinations of these growth rates. There was close agreement between observed and simulated absolute treatment means for fatness, except when animals were fed diets low in protein. In this case, experimental animals fed inadequate protein grew at slower rates and became fatter than contemporaries fed adequate protein, whereas the model predicted the opposite. Ability of the model to predict effects of nutrition not associated with changes in BW was evaluated using the proportion of residual variation in experimental fat percentage accounted for by the model, after fitting linear and quadratic terms for empty BW. The model accounted for 13.8 to 56.2% of the residual variation in observed fatness in four experiments in which significant differences in fatness were observed among nutritional treatments after accounting for differences in empty BW. Regression of observed fatness on model-simulated fatness resulted in regression coefficients that were positive and close to 1 in these four experiments. This suggests that the model can accurately predict some of the effects of nutrition on fatness that are not associated with changes in empty BW.

Adipose Tissue↗
PubMed1998

Aortic and hepatic contrast medium enhancement at CT. Part I. Prediction with a computer model.

PURPOSE: To develop a physiologic model of contrast medium enhancement by incorporating available physiologic data and contrast medium pharmacokinetics and to predict organ-specific contrast medium enhancement at computed tomography (CT) with various contrast medium injection protocols in patients of variable height and weight. MATERIALS AND METHODS: A computer-based, compartmental model of the cardiovascular system was generated by using human physiologic parameters and more than 100 differential equations to describe the transport of contrast medium. Blood volume, extracellular fluid volume, and regional blood flow were estimated from available data. Local structures were modeled mathematically to describe the distribution and dispersion of intravascularly administered iodinated contrast medium. A global model was formed by integrating regional circulation parameters with the models of local structures. Aortic and hepatic CT contrast-enhancement curves were simulated for three protocols and were compared with mean enhancement curves in three groups of 25-28 patients (80 patients total; 28 in one group, 25 in one group, and 27 in one group) receiving the same protocols. The percent difference in maximum enhancement between the simulated and empiric curves and the enhancement difference index (sum of the area difference between the simulated and empiric curves divided by the total area under the empiric curve) were computed. RESULTS: The simulated and empiric enhancement curves closely agreed in maximum enhancement (the mean percent difference in the aorta was 7.4%; liver, 4.8%) and in variation over time (mean enhancement difference index in the aorta was 11.6%; liver, 12.7%). CONCLUSION: A computer-based, physiologic model that may help predict organ-specific CT contrast medium enhancement for different injection protocols was developed. Such a physiologic model may have many clinical applications.

Adult↗
PubMed2004

Development of a computational approach to predict blood-brain barrier permeability.

The objectives of this study were to generate a data set of blood-brain barrier (BBB) permeability values for drug-like compounds and to develop a computational model to predict BBB permeability from structure. The BBB permeability, expressed as permeability-surface area product (PS, quantified as logPS), was determined for 28 structurally diverse drug-like compounds using the in situ rat brain perfusion technique. A linear model containing three descriptors, logD, van der Waals surface area of basic atoms, and polar surface area, was developed based on 23 compounds in our data set, where the penetration across the BBB was assumed to occur primarily by passive diffusion. The correlation coefficient (R(2)) and standard deviation (S.D.) of the model-predicted logPS against the observed are 0.74 and 0.50, respectively. If an outlier was removed from the training data set, the R(2) and S.D. were 0.80 and 0.44, respectively. This new model was tested in two literature data sets, resulting in an R(2) of 0.77 to 0.94 and a S.D. of 0.38 to 0.51. For comparison, four literature models, logP, logD, log(D. MW(-0.5)), and linear free energy relationship, were tested using the set of 23 compounds primarily crossing the BBB by passive diffusion, resulting in an R(2) of 0.33 to 0.61 and a S.D. of 0.59 to 0.76. In summary, we have generated the largest PS data set and developed a robust three-descriptor model that can quantitatively predict BBB permeability. This model may be used in a drug discovery setting to predict the BBB permeability of new chemical entities.

Algorithms↗
PubMed2000

Predictive value of computed tomographic myelography in obstetrical brachial plexus palsy.

Preoperative radiologic studies to detect root avulsions of the brachial plexus caused by birth trauma are considered useful in assisting with surgical planning for reconstruction. In this study, the predictive value of computed tomographic (CT) myelography in detecting nerve root avulsions at our institution was determined. Sixty-three consecutive patients with an obstetrical brachial plexus palsy who had had both preoperative CT myelography and reconstructive surgery were selected. All CT myelograms were analyzed post hoc by a single neuroradiologist in a manner blind to the surgical findings. At each root level of the brachial plexus, the presence of a pseudomeningocele was noted along with the presence or absence of rootlets within each identified pseudomeningocele. Extraforaminal root avulsions later determined at surgery were reviewed by a single surgeon in a manner blind to the radiographic results. Surgical and radiographic findings were then compared at each corresponding root level. A total of 281 roots were examined. The sensitivity, specificity, positive predictive value, and likelihood ratio for root avulsions with pseudomeningoceles were 0.63, 0.85, 0.40, and 4.2, respectively. For pseudomeningoceles for which rootlets traversing the sac could not be identified, these values were 0.37, 0.98, 0.74, and 18.5, respectively. The presence of pseudomeningoceles with or without rootlets was not a sensitive indicator of root avulsions. Root avulsions were better predicted by identifying the absence of rootlets in a pseudomeningocele. This absence on CT myelography may be used to suggest an extraforaminal root avulsion due to its high specificity and high likelihood ratio.

Birth Injuries↗
PubMed2003

The high value of high-resolution computed tomography in predicting the activity of pulmonary tuberculosis.

SETTING: A 2500-bed medical centre in southern Taiwan. OBJECTIVE: To study the clinical value of high-resolution computed tomography (HRCT) in predicting the activity of pulmonary tuberculosis (TB). DESIGN: HRCTs were performed prospectively in 148 patients whose chest radiographs (CXRs) showed highly suspicious signs of pulmonary TB, predominantly upper lung field infiltration. The HRCT findings, interpreted independently by a pulmonologist and a radiologist, were used to predict the activity of pulmonary TB. RESULTS: Pulmonologist-interpreted and radiologist-interpreted HRCTs showed high sensitivity (both 93%), specificity (83 vs. 88%), accuracy (86 vs. 90%), positive predictive values (76 vs. 83%) and negative predictive values (both 95%). Kappa statistic indicates good inter-reader agreement. CONCLUSION: HRCT has a high value in predicting the activity of pulmonary TB. It is a useful tool in this regard when a patient with suspected pulmonary TB lacks microbiologic proof, when clinical condition makes invasive diagnosis impossible or when a patient has completed anti-tuberculosis treatment with no compatible unequivocal CXR.

Adult↗
PubMed1995

RNA secondary structure prediction using highly parallel computers.

An RNA secondary structure prediction method using a highly parallel computer is reported. We focus on finding thermodynamically stable structures of a single-stranded RNA molecule. Our approach is based on a parallel combinatorial method which calculates the free energy of a molecule as the sum of the free energies of all the physically possible hydrogen bonds. Our parallel algorithm finds many highly stable structures all at once, while most of the conventional prediction methods find only the most stable structure. The important idea in our algorithm is search tree pruning, with dynamic load balancing across the processor elements in a parallel computer. Software tools for visualization and classification of secondary structures are also presented using the sequence of cadang-cadang coconut viroid as an example. Our software system runs on CM-5.

Algorithms↗
PubMed1997

A prognostic computer model to predict individual outcome in interventional cardiology. The INTERVENT Project.

It is not yet possible to predict an individual's outcome from percutaneous transluminal coronary angioplasty or alternative/adjunctive coronary interventional techniques. The purpose of the INTERVENT project is to redefine complications associated with coronary interventions, to set up a prognostic computer model to predict individual outcome and to compare the results to those of conventional statistical techniques. 2500 data items were analysed in 455 consecutive patients (mean age: 61.1 +/- 8.3 years; range 33-84 years; 80.4% male, 16.7% unstable angina, 5.1%/10.1% acute/subacute myocardial infarction) undergoing coronary interventions at three university centres. In-lab/out-of-lab complication rates were 0.4%/0.9% (death), 1.8%/0.2% (abrupt vessel closure with myocardial infarction) and 5.5%/4.0% (haemodynamic complications). Computer algorithms derived by applying techniques from artificial intelligence were able (1) to reduce the set of possible relevant risk factors from 2500 to about 40, (2) to predict individual risk with an accuracy of > 95% and (3) to explain the structural relationship between outcome and risk factors. Patient data from two centres were used to construct and test the algorithm. Data from a third centre were used to evaluate the algorithm. The most important predictors-were acute myocardial infarction, heart failure (NYHA class > II), unstable angina, complex lesions, high low density lipoprotein cholesterol and duration of coronary heart disease. Neither age nor gender impaired the percutaneous transluminal coronary angioplasty results in acute ischaemic syndromes; however, for stable angina, procedural risk increased with age. There was little risk from primary percutaneous transluminal coronary angioplasty in acute myocardial infarction in patients with NYHA heart failure classes I-II; however, the risk was high for patients in NYHA classes > II, either with or without additional thrombolysis. Alternative/adjunctive intervention techniques were no predictors for in-lab-, but were predictors for post-procedural complications.

Adult↗
PubMed1994

Thin-section contrast-enhanced computed tomography accurately predicts the resectability of malignant pancreatic neoplasms.

A prospective diagnostic study was designed to determine the ability of thin-section contrast-enhanced computed tomography (CT) to predict the resectability of malignant neoplasms of the pancreatic head. Patients with a presumed resectable pancreatic neoplasm referred during a 21-month period were studied with abdominal CT performed at 1.5-mm section thickness and 5-mm slice interval during the bolus phase of intravenous contrast enhancement. CT criteria for resectability included the absence of extrapancreatic disease, no evidence of arterial encasement, and a patent superior mesenteric-portal venous confluence. Of 145 patients evaluated, 42 were considered to have resectable tumors by CT criteria, and 37 (88%) underwent potentially curative pancreaticoduodenectomy. Six patients were found to have a microscopically positive retroperitoneal resection margin; no patient had a grossly positive resection margin. Five (12%) of 42 patients were found at laparotomy to have unresectable, locally advanced or metastatic tumors. Thin-section contrast-enhanced CT is an essential component of the preoperative evaluation for pancreaticoduodenectomy and can prevent needles laparotomy in most patients with locally advanced or metastatic disease.

Adenocarcinoma↗
PubMed2002

Experimental and computational screening models for prediction of aqueous drug solubility.

PURPOSE: To devise experimental and computational models to predict aqueous drug solubility. METHODS: A simple and reliable modification of the shake flask method to a small-scale format was devised, and the intrinsic solubilities of 17 structurally diverse drugs were determined. The experimental solubility data were used to investigate the accuracy of commonly used theoretical and semiexperimental models for prediction of aqueous drug solubility. Computational models for prediction of intrinsic solubility, based on lipophilicity and molecular surface areas, were developed. RESULTS: The intrinsic solubilities ranged from 0.7 ng/mL to 6.0 mg/ mL, covering a range of almost seven log10 units, and the values determined with the new small-scale shake flask method agreed well with published solubility data. Solubility data computed with established theoretical models agreed poorly with the experimentally determined solubilities, but the correlations improved when experimentally determined melting points were included in the models. A new, fast computational model based on lipophilicity and partitioned molecular surface areas, which predicted intrinsic drug solubility with a good accuracy (R2 of 0.91 and RMSEtr of 0.61) was devised. CONCLUSIONS: A small-scale shake flask method for determination of intrinsic drug solubility was developed, and a promising alternative computational model for the theoretical prediction of aqueous drug solubility was proposed.

Chemical Phenomena↗