Estimating product bioequivalence for highly variable veterinary drugs.

The occurrence of drugs and drug formulations associated with large intrasubject pharmacokinetic (PK) variability has been well described in humans and is likewise encountered in veterinary medicine. The scaled average bioequivalence (SABE) approach adopted by CDER of the FDA for the determination of bioequivalence (BE) of highly variable drugs (HVD) needs to be considered when applied to veterinary dosage forms. However, because of some of the unique challenges that are encountered within the framework of veterinary medicine, variations of CDER's approach are presented. The present manuscript discusses HVD and highly variable veterinary drugs (HVVD) from the perspective of possible alternative approaches to support the assessment of product BE in veterinary medicine. Limitations in the use of 3- and 4-way crossover study designs are enumerated. In addition to a need for a statistical analysis of HVVD when using a parallel study design, the use of the secondary criteria (test-to-reference ratio), definition of σ(0) , and average BE with expanding limits are raised. A number of the details need to be finalized, from the selection of a regulatory constant to the determination of 'highly variable' in a veterinary drug product. Academicians, industrial scientists, and regulators should continue this discussion and resolve these details.

Exploration of developmental approaches to companion animal antimicrobials: providing for the unmet therapeutic needs of dogs and cats.

The American Academy of Veterinary Pharmacology and Therapeutics (AAVPT) and the United States Pharmacopeia (USP) co-sponsored a workshop to explore approaches for developing companion animal antimicrobials. This workshop was developed in response to the shortage of antimicrobials labeled for dogs and cats, as there is a shortage of approved antimicrobials for the range of infectious diseases commonly treated in small animal practice. The objective of the workshop was to identify alternative approaches to data development to support new indications consistent with the unmet therapeutic needs of dogs and cats. The indications for currently approved antimicrobials do not reflect the broader range of infectious diseases that are commonly diagnosed and treated by the veterinarian. Therefore, the labels for these approved antimicrobials provide limited information to the veterinarian for appropriate therapeutic decision-making beyond the few indications listed. Industry, veterinary practice, and regulatory challenges to the development of new antimicrobial indications were discussed. The workshop resulted in short- and long-term recommendations. Short-term recommendations focus on the use of additional data considerations for product labeling. Long-term recommendations center on legislative or regulatory legal initiatives. The workshop recommendations will need collaboration from industry, academia, and regulatory authorities and a legal shift in the drug approval and availability processes.

Reactive carbonyl formation by oxidative and non-oxidative pathways.

The spectrophotometric protein carbonyl assay is used as an indicator of protein damage by free radical reactions in vitro and in a variety of pathologies. We investigated model proteins and a variety of oxidative and non-oxidative reactions, as well as what effects hemoglobin, myoglobin, and cytochrome c might have on levels of protein carbonyls. We show that oxidative as well as non-oxidative mechanisms introduce carbonyl groups into proteins, providing a moiety for quantification with 2,4-dinitrophenylhydrazine (DNPH). Bovine serum albumin exposed to oxidative scenarios, such as hypochlorous acid, peroxynitrite, and metal-catalyzed oxidation exhibited variable, but increased levels of carbonyls. Other non-oxidative modification systems, in which proteins are incubated with various aldehydes, such as malondialdehyde, acrolein, glycolaldehyde, and glyoxal also generated significant amounts of carbonyls. Furthermore, purified myoglobin, hemoglobin, and cytochrome c show high absorbance at the same wavelengths as DNPH. The high levels observed are due to the innate absorbance of hemoglobin, myoglobin, and cytochrome c near the assay spectra of DNPH. These studies show that carbonyl content could be due to oxidative as well as non-oxidative mechanisms and that heme-containing compounds may effect carbonyl quantification.

Industrial buyers' perception of effective selling'.

The most fundamental aspect of commerce is interaction between buyers and sellers. Accordingly, the psychological study of selling techniques can be considered as old as trade. This study investigated two categories of selling techniques composed of 17 objection-addressing and 13 sale-dosing strategies. Reported are survey responses from 242 industrial buyers, frequent targets of selling techniques, who were asked to identify which technique from each category they associated with salespersons' effective selling behavior.

Relationship of birth order and the marketing-related variable of materialism.

The relationship between the birth order and materialism scores was investigated using materialism conceptualized as a consumer value. Data were collected from 275 alumni of a major southwestern university. The analysis indicated that first-borns in this sample scored significantly lower on materialism than younger siblings.

Birth order and two marketing-related measures of aggression.

Several bodies of research link birth order and aggression. With a sample of 144 women and 225 men business students, the present study investigated birth order and aggression using two measures from academic marketing. Neither measure detected significant influence of birth order. Implications are discussed regarding marketing and consumers' behavior.

Efficacy of etodolac for the treatment of osteoarthritis of the hip joints in dogs.

OBJECTIVE: To assess the efficacy of etodolac in improving hind limb function in dogs with osteoarthritis of the hip joint. DESIGN: Prospective study. ANIMALS: 100 client-owned dogs with clinical signs of osteoarthritis of the hip joint. PROCEDURE: Baseline ground reaction forces and subjective assessment scores were collected twice at a 7- to 10-day interval. After meeting entrance criteria, dogs were randomly assigned to the following 3 treatment groups: control group (0 mg of etodolac), low-dosage group (135 mg of etodolac), or high-dosage group (450 mg of etodolac). Dogs were treated once daily for 8 days, and gait analysis was repeated on day 8. RESULTS: On day 8 of treatment, vertical impulse and vertical peak force values for low- and high-dosage groups were significantly greater than baseline values within each group. On day 8, vertical impulse values from the high-dosage group were significantly greater than values from the low-dosage group. Vertical peak forces for the low- and high-dosage groups were significantly greater at 8 days than that of the control group. Analysis of the effect of evaluation center (site) on treatment outcome did not reveal a significant effect. CLINICAL IMPLICATIONS: Etodolac administration for 8 days improved ground reaction forces in dogs with osteoarthritis of the hip joint. Improvement in force transmission was dosage dependent for the primary outcome measurement (vertical impulse). Results of the study indicate that etodolac is well tolerated by dogs, with minimal adverse effects during an 8-day treatment period.

Psychological distress and burnout among buddies: demographic, situational and motivational factors.

Work-related psychological distress (burnout) is a probable cause of drop-out among emotional support volunteers (buddies) who work with people living with AIDS. In addition to the emotional suffering and disruption to both the buddy and the buddied, burnout has significant cost implications for voluntary organizations in terms of training and recruitment. The aim of this study was to identify the demographic, situational and motivational factors associated with burnout among buddies with the intention of identifying individuals at risk at the recruitment stage. A cross-sectional single cohort postal questionnaire study design was used. All buddies registered with the Terrence Higgins Trust, a non-profit making organization set up in the UK to provide education about HIV/AIDS and care for people affected by the virus, were invited to participate. Psychological morbidity was measured with the Hospital Anxiety and Depression Scale, burnout with the Maslach Burnout Inventory and motivation was assessed using the Calvert Motivation Checklist. Information on the buddy relationship and the demographic details of each buddy was also collected. Of 586 questionnaires distributed, 324 (55%) were returned. More than 24% of buddies were classified as probable cases of burnout on one or more of the MBI scales but this is lower than has been reported in medical and nursing staff working with people living with AIDS. Although a number of demographic, situational and motivational factors were associated with burnout, logistic regression models were unable to identify a useful proportion of individuals at risk. It was concluded that although burnout is an important psychological factor in retaining volunteers, it was not possible to identify individuals at risk of burning out either from their self-reported motivations or from demographic factors.

Welcoming AIDS education.

As paediatric nurses working with children and their families who are living with HIV and AIDS, we welcome the recent decision to include HIV and AIDS the schools' National Curriculum.