AAPS PharmSci

The first objective of this study was to assess the existence of nonresponse bias to a national survey of licensed pharmacists conducted in 2000. Three methods were used to assess nonresponse bias. The second objective of the study was to examine reasons why sampled licensed pharmacists did not respond to the national survey of licensed pharmacists. We used data from 2204 respondents to a national survey of pharmacists and from 521 respondents to a survey of nonrespondents to the national survey. We made comparisons between respondents for 5 variables: employment status, gender, age, highest academic degree, and year of initial licensure. Chi-square tests were used to examine differences in the 5 variables between respondents to the first mailing and second mailing of the survey, early and late respondents to the survey, and respondents to the survey and respondents to the nonrespondent survey. There were no significant differences between first mailing and second mailing respondents, but there were differences in each variable except year of licensure between early and late respondents. These differences likely were due to regional bias possibly related to differences in mailing times. There were differences between respondents and nonrespondents in terms of employment status and year of licensure. The main reasons for not responding to the survey were that it was too long or that it was too intrusive. Overall, the survey methodology resulted in a valid sample of licensed pharmacists. Nonresponse bias should be assessed by surveying nonrespondents. Future surveys of pharmacists should consider the length of the survey and the address where it is sent.

Caco-2 cell permeability was evaluated in isotonic media containing high (25mM) or physiological (5.5mM) glucose concentrations. Transepithelial electrical resistance (TEER) and membrane fluidity were measured to assess glucose-induced alterations in physical barrier properties. In parallel, distribution of the actin filament (F-actin) and zonula occludens-1 (ZO-1) proteins was assessed by confocal microscopy. Transepithelial fluxes of mannitol, hydrocortisone, digoxin, and glycyl sarcosine (Gly-Sar) that permeate the intestinal mucosa by various pathways were measured to quantify the effect of glucose-induced changes on Caco-2 cell permeability. High glucose decreased maximum TEER of cell monolayers by 47%, whereas membrane fluidity at the hydrophobic core and lipid/polar head interphase was significantly increased. F-actin distribution in high glucose cells appeared more diffuse while ZO-1 was unchanged. Mannitol and hydrocortisone fluxes across Caco-2 cells cultured in high glucose increased by 65% and 24%, respectively. In addition, high glucose decreased the maximum transport capacity (Vmax) of PepT-1. P-glycoprotein activity, however, was unchanged. In conclusion, high extracellular glucose concentration in isotonic media significantly alters physical barrier properties of Caco-2 cell monolayers, which predominantly affects transepithelial transport of solutes permeating the cell barrier by paracellular and transcellular passive diffusion and facilitated transport mediated by the proton-dependent oligopeptide transporter (PepT-1).

Residues are composed of the parent drug and metabolites, and therefore interspecies comparisons must involve a consideration of comparative xenobiotic metabolism. The focus of this article will be the residue studies that are required to establish human food safety, and the interspecies pharmacokinetic differences and similarities that impact drug residues in animal- derived foods. To illustrate the factors that can complicate and assist these comparisons, 2 drugs will be examined in detail: ivermectin and fenbendazole. In addition, the activities of 2 US programs, the Food Animal Residue Avoidance Databank (FARAD) and the NRSP-7 (National Research Support Project Number 7) Minor Use Animal Drug Program will be presented, along with strategies that may be employed in the study of species differences.

In this study, the effect of powder cellulose (PC) and 2 types of microcrystalline cellulose (MCC 101 and MCC 301) on pellet properties produced by an extrusion/spheronization process was investigated. The different investigated types of cellulose displayed different behavior during the extrusion/spheronization process. Pure PC was unsuitable for extrusion, because too much water was required and the added water was partly squeezed during the extrusion process. In contrast, MCC 101 and MCC 301 were extrudable at a wide range of water content, but the quality of the resulting products varied. In the extrusion/spheronization process, MCC 101 was the best substance, with easy handling and acceptable product properties. The properties of the extrudates and pellets were determined by Fourier transform (FT) Raman spectroscopy and environmental scanning electron microscopy (ESEM). FT-Raman spectroscopy was able to distinguish between the original substances and also between the wet and dried extrudates. The particle sizes of the raw material and of the extrudates were determined by ESEM without additional preparation. For MCC, the size of the resulting particles within the extrudate or pellet was smaller. However, in the extrudates of PC, changes in particle size could not be observed.

We have observed that certain C-and N-glucuronides prepared as intermediates for breast cancer preventives demonstrate non-first order 1H NMR spectra that are not the result of impurities or degradation but are instead due to virtual coupling in the pyran proton network. This virtual coupling shows the expected dependence on solvent and field strength and, more importantly, on the nature of the C-1 substitution. Although the hybridization of the atom bonded to C-1 may play a role, it appears that steric and/or electronic factors, which have the effect of increasing Δv/J for H-3 and H-4, are critical for eliminating the spectral complexity. These observations, which appear to be fairly general, suggest that this phenomenon should be considered when addressing the purity of pharmaceutical agents containing these types of structural units.

The use of pharmacogenomics to individualize drug therapy offers the potential to improve drug effectiveness, reduce adverse side effects, and provide cost-effective pharmaceutical care. However, the combinations of disease, drug, and genetic test characteristics that will provide clinically useful and economically feasible therapeutic interventions have not been clearly elucidated. The purpose of this paper was to develop a framework for evaluating the potential cost-effectiveness of pharmacogenomic strategies that will help scientists better understand the strategic implications of their research assist in the design of clinical trials, and provide a guide for health care providers making reimbursement decisions. We reviewed concepts of cost-effectiveness analysis and pharmacogenomics and identified 5 primary characteristics that will enhance the cost-effectiveness of pharmacogenomics: 1) there are severe clinical or economic consequence that are avoided through the use of pharmacogenomics, 2) monitoring drug response using current methods is difficult, 3) a well-established association between genotype and clinical phenotype exists, 4) there is a rapid and relatively inexpensive genetic test, and 5) the variant gene is relatively common. We use this framework to evaluate several examples of pharmacogenomics. We found that pharmacogenomics offers great potential to improve patients' health in a cost-effective manner. However, pharmacogenomics will not be applied to all currently marketed drugs, and careful evaluations are needed on a case-by-case basis before investing resources in research and development of pharmacogenomic-based therapeutics and making reimbursement decisions.