A provisional biopharmaceutical classification of the top 200 oral drug products in the United States, Great Britain, Spain, and Japan

Orally administered, immediate-release (IR) drug products in the top 200 drug product lists from the United States (US), Great Britain (GB), Spain (ES), and Japan (JP) were provisionally classified based on the Biopharmaceutics Classification System (BCS). The provisional classification is based on the aqueous solubility of the drugs reported in readily available reference literature and a correlation of human intestinal membrane permeability for a set of 29 reference drugs with their calculated partition coefficients. Oral IR drug products constituted more that 50% of the top 200 drug products on all four lists, and ranged from 102 to 113 in number. Drugs with dose numbers less than or equal to unity are defined as high-solubility drugs. More than 50% of the oral IR drug products on each list were determined to be high-solubility drugs (55-59%). The provisional classification of permeability is based on correlations of the human intestinal permeabilities of 29 reference drugs with the calculated Log P or CLogP lipophilicity values for the uncharged chemical form. The Log P and CLogP estimates were linearly correlated (r2 = 0.79) for 187 drugs. Metoprolol was chosen as the reference compound for permeability and Log P or CLogP. A total of 62-69.0% and 56-60% of the drugs on the four lists exhibited CLogP and Log P estimates, respectively, greater than or equal to the corresponding metoprolol value and are provisionally classified as high-permeability drugs. We have compared the BCS classification in this study with the recently proposed BDDCS classification based on fraction dose metabolism. Although the two approaches are based on different in vivo processes, fraction dose metabolized and fraction dose absorbed are highly correlated and, while depending on the choice of reference drug for permeability classification, e.g., metoprolol vs cimetidine or atenolol, show excellent agreement in drug classification. In summary, more than 55% of the drug products were classified as high-solubility (Class 1 and Class 3) drugs in the four lists, suggesting that in vivo bioequivalence (BE) may be assured with a less expensive and more easily implemented in vitro dissolution test.     

Spontaneous intracranial hypo and hypertensions: an imaging review

Cerebrospinal fluid (CSF) pressure changes can manifest as either intracranial hypertension or hypotension. The idiopathic forms are largely under or misdiagnosed. Spontaneous intracranial hypotension occurs due to reduced CSF pressure usually as a result of a spontaneous dural tear. Idiopathic intracranial hypertension (IIH) is a syndrome of elevated intracranial tension without hydrocephalus or mass lesions and with normal CSF composition. Neuroimaging plays an important role in excluding secondary causes of raised intracranial tension. As the clinical presentation is varied, imaging may also help the clinician in arriving at the diagnosis of IIH with the help of a few specific signs. In this review, we attempt to compile the salient magnetic resonance imaging findings in these two conditions. Careful observation of these findings may help in early accurate diagnosis and to provide appropriate early treatment.     

Vascular decomposition using weighted approximate convex decomposition

Objective

Stroke treatment often requires analysis of vascular pathology evaluated using computed tomography (CT) angiography. Due to vascular variability and complexity, finding precise relationships between vessel geometries and arterial pathology is difficult. A new convex shape decomposition strategy was developed to understand complex vascular structures and synthesize a weighted approximate convex decomposition (WACD) method for vascular decomposition in computer-aided diagnosis.

Materials and methods

The vascular tree is decomposed into optimal number of components (determined by an expert). The decomposition is based on two primary features of vascular structures: (i) the branching factor that allows structural decomposition and (ii) the concavity over the vessel surface seen primarily at the site of an aneurysm. Such surfaces are decomposed into subcomponents. Vascular sections are reconstructed using CT angiograms. Next the dual graph is constructed, and edge weights for the graph are computed from shape indices. Graph vertices are iteratively clustered by a mesh decimation operator, while minimizing a cost function related to concavity.

Results

The method was validated by first comparing results with an approximate convex decomposition (ACD) method and next on vessel sections (n = 177) whose number of clusters (ground truth) was predetermined by an expert. In both cases, WACD produced promising results with 84.7 % of the vessel sections correctly clustered and when compared with ACD produced a more effective decomposition. Next, the algorithm was validated in a longitudinal study data of 4 subjects where volumetric and surface area comparisons were made between expert segmented sections and WACD decomposed sections that contained aneurysms. The results showed a mean error rate of 7.8 % for volumetric comparisons and 10.4 % for surface area comparisons.

Conclusion

Decomposition of the cerebral vasculature from CT angiograms into a geometrically optimal set of convex regions may be useful for computer-assisted diagnosis. A new WACD method capable of decomposing complex vessel structures, including bifurcations and aneurysms, was developed and tested with promising results.