The global population is aging. In many industrial countries, almost one in five people are over age 65. As people age, gradual changes ensue in vision, hearing, balance, coordination, and memory. Products, communication materials, and the physical environment must be thoughtfully designed to meet the needs of people of all ages. This article summarizes normal changes in sensory function, mobility, balance, memory, and attention that occur with age. It presents practical guidelines that allow design professionals to accommodate these changes and better meet the needs of older adults. Designing for older adults is inclusive design: it accommodates a range of physical and cognitive abilities and promotes simplicity, flexibility, and ease of use for people of any age.

No abstract

Recent advances in in vitro metabolism methods have led to an improved ability to predict clinically relevant metabolic drug-drug interactions. To address the relationships of in vitro metabolism data and in vivo metabolism outcomes, the Office of Clinical Pharmacology and Biopharmaceutics in the Center for Drug Evaluation and Research, Food and Drug Administration, evaluated a number of recently approved new drug applications. The goal of these evaluations was to determine the contribution of in vitro metabolism data in (1) predicting in vivo drug-drug interactions, (2) determining the need to conduct an in vivo drug-drug interaction study, and (3) incorporating findings into drug product labeling. Ten cases are presented in this article. They fall into two major groups: (1) in vitro data were predictive of in vivo results, and (2) in vitro data were not predictive of in vivo results. Discussion of these cases highlights factors limiting predictability of in vivo metabolic interactions from in vitro metabolism data. The integration of these findings into drug product labeling is also discussed.

Nemonoxacin (TG-873870) is a novel nonfluorinated quinolone with potent broad-spectrum activity against Gram-positive and Gram-negative pathogens, including methicillin-resistant Staphylococcus aureus, penicillinand quinolone-resistant Streptococcus pneumoniae, and vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus. The safety, tolerability, and pharmacokinetics of nemonoxacin were investigated in a double-blind, ascending-single-dose study involving 56 healthy subjects (48 males and 8 females) who were randomly assigned to 1 of 7 dose cohorts. In each successive cohort, two subjects received a placebo and six received single oral doses of 25, 50, 125, 250, 500, 1,000, or 1,500 mg nemonoxacin. Nemonoxacin was well tolerated up to the maximum dose of 1,500 mg. No severe or serious adverse events were observed. The most frequent adverse events were contact dermatitis, pruritus, and erythema. No clinically significant abnormalities were noted in the electrocardiograms, vital signs, or laboratory tests. The plasma concentrations increased over the dose range, and at 500 mg, the free area under the plasma concentration-time curve/MIC 90 ratios and free maximum nemonoxacin concentration/MIC 90 ratios against drug-sensitive/drug-resistant S. pneumoniae and S. aureus were greater than 227 and 24, respectively. The peak time and elimination half-life of nemonoxacin were 1 to 2 h and 9 to 16 h, respectively. The oral clearance was approximately 0.22 liter/h/kg. The plasma protein binding was approximately 16%. The results of this study support further evaluation of the multiple-dose safety, tolerability, and pharmacokinetics of nemonoxacin.Newer-generation quinolones are largely fluoroquinolones (FQs); they are characterized by the presence of a fluorine at the R6 position of the quinolone nucleus (2, 9, 19). Owing to their improved activity against Gram-positive and atypical pathogens, they have been widely used for the treatment and prophylaxis of bacterial infections. However, the use of FQs has been compromised by the emergence of bacterial resistance (3,8,14,18,22,30) and the potential for adverse side effects (15, 21), including ECG QTc interval prolongation, hepatotoxicity, and phototoxicity. Thus, there is an unmet need for newer compounds that are broad-spectrum agents effective against existing bacterial resistance and that have the potential to minimize the risk of use-limiting adverse effects.Nemonoxacin (TG-873870) (36), a novel nonfluorinated quinolone, has recently been developed from a series of 8-methoxy nonfluorinated quinolones (29) as a malate salt. It differs from FQs in that it lacks the fluorine at the R6 position (Fig. 1); this was formerly believed to be important for the antibacterial potency of FQs. Nemonoxacin has demonstrated broadspectrum activity (4, 20, 28) against Gram-positive, Gramnegative, and atypical pathogens. Furthermore, nemonoxacin appears to be more potent than several FQs, including ciprofloxacin, levofloxacin, and moxifloxacin (20). In preclinical studies, ...

A total of 194 new molecular entities approved by the Food and Drug Administration between 1992 and 1997 were surveyed to determine the role of in vitro metabolic interactions in the conduct of drug-drug interaction studies and to examine the methods used in these studies. Approximately 30% of the submissions were found to have in vitro metabolism-based interaction studies, most of which were inhibitory in nature. Chemical inhibition was the most commonly used approach in studying drug interactions in vitro. In this article, an attempt to assess the quality of the chemical inhibition approach was made. Four areas were found to be often overlooked: (1) incubation time and concentrations of the drug, (2) the difference between inhibition constant (k(i)) and 50% inhibitory concentration (IC50) values, (3) the substrate-dependent inhibition potential, and (4) the metabolic genotype or phenotype of the liver donor. We discuss the pitfalls in estimating drug interactions when these four areas are overlooked.