The Rate and Extent of Oral Bioavailability versus the Rate and Extent of Oral Absorption: Clarification and Recommendation of Terminology

In the literature, the meanings of the terms oral absorption and oral bioavailability of drugs vary greatly. Absorption has been considered to take place at the mucosal membrane of the gastrointestinal (GI) tract. It has also been defined as the process from the site of drug administration to the site of measurement. In the latter definition, the extent of oral absorption depends on the extent of first-pass elimination in the gut wall and liver even though a drug may be completely absorbed from the GI tract. Moreover, these two terms have also been used interchangeably. Inconsistency in the definition of these two terms has led to varying interpretations of these terms among students, researchers and laymen, and such an inconsistency seems undesirable. Apparently because of these inconsistencies, improper correlations between the Caco-2 permeability or intestinal permeability and the oral bioavailability of drugs subject to extensive first-pass effect may have occurred. It is suggested that absorption be defined as movement of drug across the outer mucosal membranes of the GI tract, while bioavailability be defined as availability of drug to the general circulation or site of pharmacological actions. Since transit times (this may range from about 1 min to several hours) across enterocytes, liver, lungs, and the peripheral venous sampling tissue are virtually unknown for all drugs, this factor alone would favor the use of oral bioavailability rate rather than oral absorption rate in all routine studies.     

The comparative effects of drive and test stimulus intensity on myocardial excitability and vulnerability

The number and intensity of stimuli that set basic cycle length in cardiac electrophysiological studies can influence the electrical properties assessed by extrastimuli. The relative contribution of drive (S1) and test (S2) stimulus intensity in defining myocardial excitability and vulnerability has not been reported. The purpose of this investigation was to assess this interaction and to determine whether atrial and ventricular findings differed. The effects of S1 and S2 intensity on atrial and ventricular stimulus-intensity-refractory-period curves were determined in open-chest dogs: comparisons were made between curves with S1 intensity varied between diastolic threshold (DT) and 10 mA and S2 intensity maintained at DT and those with S1 intensity maintained at DT and S2 intensity varied between DT and 10 mA. S1-S1 was held constant and S1-S2 varied. The effects of different stimulation sites, cycle length, number of stimulations, and neural blockade were assessed. S1 intensity amplification shifted atrial stimulus-intensity-refractory period curves in the direction of increased excitability and vulnerability; the changes were more pronounced than those obtained by modulating S2 intensity. The changes produced by increasing S1 intensity were evident at different cycle lengths and were enhanced by an increased number of stimulations, but were not evident when S1 and S2 were delivered at different atrial sites. Although beta-blockade attenuated the effects of increasing S1 intensity somewhat, the addition of cholinergic blockade virtually abolished it. Ventricular refractoriness was also changed by modulation of S1 intensity, but the changes were less striking. In the atrium, modulation of S1 intensity has greater effects of stimulus-intensity-refractory-period relations than modulation of S2 intensity; in the ventricule, the converse is true.     

Notified tuberculosis among Singapore residents by ethnicity, 2002–2011

Setting:

The National Tuberculosis Programme in Singapore where, among resident cases, higher tuberculosis (TB) rates have been reported in ethnic Malays.

Objective:

To describe the socio-demographic and clinical characteristics of resident TB cases by ethnicity, and to assess whether Malays differ from other groups in terms of the above parameters.

Design:

Cross-sectional review of records from the tuberculosis registry’s electronic database.

Results:

Among 15 622 resident cases notified, 72.2% were Chinese, 18.7% Malay, 5.8% Indian and 2.9% were from other minorities. Compared to other ethnicities, Malays were more likely to be incarcerated at the time of notification (odds ratio [OR] 3.70, 95%CI 3.03–4.52) and clustered at the same residential address (OR 1.65, 95%CI 1.44–1.89), but were less likely to be aged ≥65 years (OR 0.61, 95%CI 0.54–0.70) or to reside in high-cost housing (OR 0.11, 95%CI 0.07–0.17). In terms of disease characteristics, more Malays had diabetes mellitus (OR 1.54, 1.37–1.73), a highly-positive acid-fast bacilli smear (OR 1.64, 95%CI 1.47–1.83) and cavitary disease on chest X-ray (OR 1.41, 95%CI 1.28–1.55).

Conclusion:

Compared to other ethnicities, reported TB cases among Malays were more severe and were likely to be more infectious. Increased vigilance in case management and contact investigations, as well as an improvement in the socio-economic conditions of this community, are required to reduce TB rates in this ethnic group.     

Platelet apheresis for digital gangrene due to thrombocytosis in chronic myeloid leukaemia.

Thrombocytosis is a frequent presenting feature of myeloproliferate disorders and is associated with increased incidence of thrombotic and haemorrhage complications. However, these complications are rare in chronic myeloid leukaemia (CML). We describe a case of CML which presented with digital gangrene due to thrombocytosis. Reduction of the platelet count by plateletpheresis lead to rapid symptomatic relief and recovery from the gangrene.     

Taurine analogues; a new class of therapeutics: retrospect and prospects

Taurine was discovered more than two hundred years ago from animal sources. It is distributed in both mammals and non-mammals and its content is high in several tissues. For more than a century-and-a-half, taurine was regarded just as an end product of sulfur metabolism. Recently, taurine has been rediscovered and its beneficial effects in processes like epilepsy, hypertension, congestive heart failure and diabetes have been well-documented. It was patented and found some clinical utility, but being an amino acid, therapeutic use confronts limitations like restricted permeability and more. This necessitates the development of pro-drugs (analogues) mainly derivatives of taurine. A large number of taurine derivatives have been reported in the literature with partial to marked activity. Taurine derivatives like taltrimide, acamprosate and tauromustine, are already in the market as anti-convulsant, anti-alcoholic and anti-cancer agents. Many other analogues are effective in experimental models. The in depth analysis of these analogues and their biological actions can provide certain clues for further consideration. In the present review, attempts have been made to provide synopsis, synthesis and symbiosis of chemical and biological actions, which may provide future guidance and facilitate further research in this area. The successful journey of these analogues to clinical utility is a healthy and happy sign and an index of bright future, and we hope that this review will provide enough input to ignite the minds.     

Consumer expectations and experiences of quality in Australian home‐based community services

Australians want to live at home as they age and seek support from health and social care services to achieve this. The consumer driven market‐based approach to community services in Australia has resulted in an increases in user's expectations of quality. What constitutes a quality service from the consumer's perspective is an important agenda to understand as the focus of care delivery moves to the domiciliary setting. This paper presents one aspect from a grounded theory PhD study, the aim of which was to understand the lived experience of receiving services in the home and its impact on the meaning of home. Participants were 11 people with dementia and 18 family supporters living in the state of Victoria, Australia. Data were collected between 2015 and 2017 through multiple interviews, photographic images, field notes and memos. NVIVO 10 qualitative analysis software program was used to support constant comparative analysis. Using a grounded theory approach, this study found that the decision to engage with community services was driven by the need to maintain autonomy, self‐identity and home life. Participants sought quality services but discovered a dichotomy of positive and negative aspects in the way services were delivered. The most common reaction to the experience of poor‐quality care was to reflect on their expectations for care quality; and manage the reality of what was delivered. Team work and service responsiveness were positive characteristics but were offset by service limitations and inefficiencies caused by poor communication and poor staff retention. The interpersonal relationships that participants developed with staff was highlighted; trust was an important factor whereas unreliable, task orientated and poorly trained staff would be rejected. The implications for policy and practice are described.     

Low intrinsic drug activity and dominant vehicle (placebo) effect in the topical treatment of acne vulgaris

In drug treatment for acne, topical products alone or in combination with systemic products are commonly prescribed. It was recently pointed out by Chiou that oral tetracyclines, the most commonly prescribed systemic drugs, may not be as effective as commonly assumed because the effect of placebo can approach drug effects during the 4 - 12 weeks of daily administration. The present work evaluated the percent contribution of vehicle (placebo) toward the reported efficacy of reduction in total (inflammatory and non-inflammatory) lesion counts of 8 commonly prescribed topical preparations at the end of 10 - 12 weeks of daily administration. These preparations included 0.1% tretinoin, 0.1% adapalene, 5% dapsone, 1% clindamycin, a combination of benzoyl peroxide with adapalene or clindamycin, and a clindamycin-tretinoin combination. The mean reduction from drugs and vehicles were 42 ± 7.1%, and 23 ± 5.0%, respectively; the mean contribution of vehicle toward drug effect was 55 ± 15% (range 35 - 82%). For 5 benzoyl peroxide preparations evaluated (2 for 2.5%, and 3 for 5.0%), their respective means were 40 ± 9%, and 25 ± 15%, and vehicle-toward-drug contribution was 58 ± 31% (range 9 - 89%). The present work shows the great importance of vehicle effects in topical therapy; in some cases this effect approached 90%. The potential significance of the above findings in the development of more effective topical anti-acne drugs was discussed.