In-use testing of extemporaneously prepared suspensions of second generation non-nucleoside reversed transcriptase inhibitors in support of phase I clinical studies.

DPC 961 and 963 are two of a series of prospective second generation non-nucleoside reverse transcriptase inhibitors (NNRTIs) being considered for the treatment of HIV infections. The 'powder in a bottle' approach was used for drug administration for Phase I clinical studies. This new approach consists of compounding the active drug as a suspension or solution at the clinical site immediately before dosing. Prior to clinical use, studies were conducted to determine the compatibility of the drugs with the suspending agent, the recovery of the drugs using the administration procedure and the dissolution profile of the suspensions. The stability of the DPC 961 and 963 in the dosing formulation was followed over a 24-h period using a stability indicating HPLC method. In addition, the dissolution profiles of the suspensions were established for future comparison with solid dosage forms. Although the two drugs have very similar chemical structures, they clearly exhibited different behaviors in liquid/liquid extraction and dissolution experiments. These differences could be related to the physical characteristics of the powders, such as particle size and surface area. The results of the in-use testing of the suspension showed adequate recovery of the drugs from the bottle at two drug levels. The stability of DPC 961 and 963 in the suspending agent was sufficient for constitution and administration of the suspensions at the clinical site.

Compartmental volumetry of the superior temporal gyrus reveals sex differences in schizophrenia--a post-mortem study.

Brain imaging studies have shown superior temporal gyrus (STG) volume loss and abnormal patterns of asymmetry in schizophrenia; however, these are not consistent findings. Post-mortem volumetry of three different STG regions (defined by external landmarks) was used to compare 17 schizophrenics to 20 age- and sex-matched controls. Total STG volumes did not differ. A significant gray-matter volume reduction in schizophrenics was observed in the middle compartment (reaching from the mamillary body to the lateral geniculate body). This may have been related to reduced length of this region, particularly in schizophrenic females. These results reflect the problematic issue of defining boundaries of macroscopic brain structures.

Financial modelling on microcomputers.

The financial modelling packages for microcomputers can be considered as falling into one of three categories:- visual spread sheets, micro base structured models and structured models which are compatible across, and allow communications between, micros and mainframes. This paper describes the three types of package, discusses the pros and cons of each, and offers a guide to system selection.