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The workshop "Bioequivalence, Biopharmaceutics Classification System, and Beyond" was held May 21-23, 2007 in North Bethesda, MD, USA. This workshop provided an opportunity for pharmaceutical scientists to discuss the FDA guidance on the Biopharmaceutics Classification System (BCS), bioequivalence of oral products, and related FDA initiatives such as the FDA Critical Path Initiative. The objective of this Summary Workshop Report is to document the main points from this workshop. Key highlights of the workshop were (a) the described granting of over a dozen BCS-based biowaivers by the FDA for Class I drugs whose formulations exhibit rapid dissolution, (b) continued scientific support for biowaivers for Class III compounds whose formulations exhibit very rapid dissolution, (c) scientific support for a number of permeability methodologies to assess BCS permeability class, (d) utilization of BCS in pharmaceutical research and development, and (e) scientific progress in in vitro dissolution methods to predict dosage form performance.

The R&D process for bringing drugs from discovery laboratories to the marketplace is undergoing rapid change, as enabled by new technologies and as demanded by the global pharmaceutical business environment. One consequence of the accelerated R&D paradigm is a blurring of the traditional discovery-development interface, which in turn impacts the traditional roles of discovery and development scientists. R&D organizations must find ways to screen out rapidly compounds that have relatively poor probability of successful registration. Quality of development candidates can be favorably influenced by early consideration of "developability" criteria along with receptor-based potency and specificity. Computational approaches and/or high-throughput experimental determinations will be used increasingly to profile compound characteristics which influence "developability." If such criteria are considered at the time of lead selection and optimization, the compound attrition rate during later development should be decreased from the historical norm. This article discusses the emerging role of development scientists during small-molecule lead selection and optimization. The changing role of development scientists also has implications for graduate curricula in the pharmaceutical sciences.

The study was conducted to assess the bioavailability of avitriptan after a standard high fat meal, in relation to gastrointestinal transit. Six healthy male subjects were enrolled in a four-period study with a partial replicate design where each was administered 150-mg avitriptan capsule (i) after an overnight fast, (ii) 5 min after a standard high-fat breakfast, and (iii) 4 hr after a standard high fat breakfast. The treatment administered in Period 3 was repeated in Period 4 to assess intrasubject variations in pharmacokinetics and gastrointestinal (GI) transit. Avitriptan capsules were specially formulated with nonradioactive 152 samarium chloride hexahydrate which was neutron-activated to gamma-emitting 153 samarium before dosing. Serial blood samples were collected for analysis of avitriptan up to 24-hr postdose, and serial scintigraphic images were obtained to assess the plasma concentration–time profile in relation to the GI transit of the avitriptan capsule contents. Bioavailability of avitriptan was reduced when administered in the fed condition but only the decrease in AUC(INF) was statistically significant Tmax was significantly delayed between the fed conditions and the fasted condition. Qualitative appearance of plasma concentration–time profiles for avitriptan could be related to the manner in which the drug emptied from the stomach. It was also apparent that avitriptan exerted a secondary pharmacologic effect that temporarily suspended gastric emptying in the fasted treatment. Thus, when gastric emptying was interrupted and then resumed, the net result was a double peak in some of the individual plasma concentration profiles. Scintigraphic analysis also demonstrated that upon emptying from the stomach, avitriptan was rapidly absorbed from the upper small intestine. In the fed state, gastric emptying was slow and continuous resulting in extended absorption and a lower occurrence of double peaks. Qualitatively, the intrasubject variability in Cmax and AUC could be explained by the intrasubject variability in gastric emptying in both fasted and fed conditions.