A process evaluation of the CREDIT (court referral and evaluation for drug intervention and treatment) pilot programme

The Court Referral and Evaluation for Drug Intervention and Treatment programme (CREDIT) was developed by a small group of magistrates at the Melbourne Magistrates' Court who wished to address the high rate of re-offending while on bail noted among illicit drug using offenders. An evaluation was conducted of the first 9 months' operation of the programme. The evaluation involved an analysis of key performance indicators (client uptake of CREDIT, retention in and satisfactory completion of treatment, the extent of re-offending while on bail) and interviews with 30 key informants and six programme participants. Despite a lack of conclusive evidence regarding the efficacy of the programme according to the identified key performance indicators, key informant interviews revealed a high level of support for the continuation of the programme.     

Delivering more effective treatment to adolescents: Improving the juvenile drug court model

Juvenile drug courts (JDC) emerged in response to a perceived need to intervene more effectively in the substance abuse-delinquency cycle. The influx of drug and alcohol offenders, lack of other juvenile justice system interventions, and positive experiences with adult drug courts helped drive interest in adapting the drug court model for juveniles. This article: (1) provides an overview of substance use and the juvenile justice system; (2) describes the current status of JDC programs; and (3) proposes a model for planning, implementing and evaluating JDCs based on adolescent drug use and treatment research as well as current JDC models. The lack of science-based JDC models and empirically sound JDC evaluations has limited the effectiveness of JDCs. The proposed model is designed to create a new generation of JDCs that maximizes the effectiveness of local resources and delivers research-based interventions to youth and families impacted by substance abuse and delinquency.     

Perspectives on non-clinical safety evaluation of drug metabolites through the JSOT workshop

The prompt and appropriate safety assessment of drug metabolite(s) was mentioned in regulatory guidances such as an International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidance, entitled "Guidance on Non-clinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals" (ICH M3(R2)) implemented in January 1 of 2011 in Japan, and has become a significant issue in the drug development. Upon release of ICH M3(R2) Step 4, a survey was conducted between March and April 2010 on the safety assessment of drug metabolites in 63 member companies of the Japan Pharmaceutical Manufacturers Association (JPMA). The Pharmacokinetics Team in the Non-Clinical Evaluation Expert Committee in JPMA conducted a questionnaire survey and compiled the results to comprehend how safety of drug metabolites are currently assessed at research-based pharmaceutical companies in Japan. The assessment of "Metabolites in Safety Testing" (MIST) can be divided into three stages based on the research purpose as follows: MIST 1 is a stage of estimating human drug metabolites and predicting their potential risks, MIST 2 is a stage of deciding the necessity for non-clinical safety studies, and MIST 3 is a stage of conducting non-clinical safety studies. In this paper, we propose typical approaches on safety assessment of metabolites that meet the purpose of each stage, considering the current level of scientific technology. Our proposals are based on the results from our survey and a symposium about the safety assessment of drug metabolites at the 37th annual meeting of the Japanese Society of Toxicology held in June 2010.     

Clinical efficacy of current transdermal drug delivery systems: a retrospective evaluation

In spite of intensive research on transdermal drug delivery systems (TDDSs), only four--nitroglycerin, clonidine, estradiol, and scopolamine--have reached the market, and the clinical effectiveness of these systems has yet to be clearly demonstrated. Ideally, a candidate for transdermal drug delivery should demonstrate clinical significance within a wide therapeutic range for a well-documented indication for use. Continuous administration of a drug should result in better control of the disease with fewer side effects and a marked increase in patient compliance than when traditional dosage forms are used. It appears that nitroglycerin is a poor candidate for transdermal drug delivery by virtue of the ambiguity associated with its clinical pharmacology, substantial interpatient variation in dose-response relationship, and development of tolerance with potential toxicity risks in chronic administration. Clonidine's well-defined indication for use coupled with its high potency and low molecular weight with high lipid solubility is well suited to transdermal therapy. Because estradiol is unsuitable for use in people who smoke and has dermatotoxic potential, it is a marginal candidate for use in TDDSs. Transdermal scopolamine was not reviewed because it is a unique entity (no conventional dosage forms of this product are available) intended for short-term use. Its use is dictated more by the patient's unique circumstances, such as travel requirements, than by physiological condition. Although TDDSs provide a convenient and effective means of administering medications, the aforementioned clinical constraints need to be evaluated in depth before more widespread application of TDDSs can be recommended. In particular; conclusive demonstration of biocompatibility of a TDDS is warranted.     

透血脑屏障制剂的研究进展

透血脑屏障的研究是药剂学研究中的一个热点和难点，目前研究较多的途径是静脉注射纳米粒和鼻腔给药。综述了纳米粒的载药方法和透血脑 屏障的机制，通过鼻腔给药实现透血脑屏障的途径，影响药物从嗅觉区进入中枢神经系统的因素以及大分子药物利用该途径的可能性。     

Versatile applications of deep eutectic solvents in drug discovery and drug delivery systems: Perspectives and opportunities

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Perspectives on antiviral drug development

The 21st International Conference on Antiviral Research provided novel insights and approaches to drug discovery across a wide array of virologic fields. Topics ranged from the chemical synthesis of new compounds against the human immunodeficiency virus (HIV) to the long-term use of established drugs against influenza. A session on novel targets for HIV therapy focused on the importance of Apobec3G, LEDGF/p75 and other cellular factors as innovative ways to control infection. New targets for hepatitis B and C viruses were surveyed. There were also discussions as to how the development of new antiviral compounds might lead to novel mechanisms of drug resistance by HIV, herpesviruses and hepatitis viruses. These covered such issues as transmission dynamics, viral fitness, the acquisition of differential resistance patterns depending on viral subtype, and clinical outcomes. Drug efficacy, toxicity, patient adherence, treatment interruption and the importance of generic drugs in resource-poor settings were also extensively discussed. These topics will all play a pivotal role in drug development and the management of viral infections in the years to come.     

Los Angeles County drug court programs: initial results

Los Angeles County established its first drug court program in 1994 in response to escalating criminal activity associated with substance abuse and overcrowded jails. This paper describes results of an evaluation of 803 drug court participants admitted to the program between 1994 and 1997. Of all drug court participants, 76% remained free of any new arrests throughout the one-year followup period, compared to 63% of participants in a drug diversion education program and 49% of the felony defendants not exposed to either program. Of offenders completing the drug court program 80% had no arrests, compared to 67% for non-completers. Drug related re-arrests were significantly lower among drug court graduates (13%) than offenders with no program participation (30%). The study results suggest that drug court participation and graduation decrease the likelihood of repeated arrests, including drug-related arrests. Drug courts represent a promising collaboration between criminal justice and public health agencies.     

Random brick model for drug transport across stratum corneum

A model for drug permeation across the stratum corneum is developed to predict the effect of the physical configuration and chemical composition of the stratum corneum on the skin permeability of drugs. The experimental data of percutaneous absorption across different skin specimens are well interpreted by the present model.     

In vitro model for evaluating drug transport across the blood-brain barrier

The passage of substances across the blood-brain barrier (BBB) is regulated in the cerebral capillaries, which possess certain distinct different morphological and enzymatic properties compared with the capillaries of other organs. Investigations of the functional characteristics of brain capillaries have been facilitated by the use of cultured brain endothelial cells, but in most studies some characteristics of the in vivo BBB are lost. To provide an in vitro system for studying brain capillary functions, we have developed a process of coculture that closely mimics the in vivo situation by culturing brain capillary endothelial cells on one side of a filter and astrocytes on the other. In order to assess the drug transport across the blood-brain barrier, we compared the extraction ratios in vivo to the permeability of the in vitro model. The in vivo and the in vitro values showed a strong correlation. The relative ease with which such cocultures can be produced in large quantities facilitates the screening of new centrally active drugs. This model provides an easier, reproducible and mass-production method to study the blood-brain barrier in vitro.     

Perspectives on pharmacy-coordinated drug administration programs

This article has described the history, operation, and impact of a pharmacy-coordinated drug administration program that existed for 20 years. It enabled pharmacy to reduce medication errors and expand its clinical role. It is not clear whether medication error rates have increased or will increase as a result of transferring this responsibility back to nursing. The clinical programs have been well established, so that their existence no longer depends on the program. Recent audit results suggest that pharmacy-nursing relations are not as good. PCUDDA programs still have a logical place in organized health care settings, particularly in view of the nursing shortage and nursing salaries. The program has clearly proven to be safe and effective and to reduce the incidence of medication errors. It is also likely to reduce cost. It is unfortunate that decisions about programs such as PCUDDA are often made on the basis of professional turf and politics rather than on patient care and economic factors, which should be the basis for such decisions.     

Statistical definition of relapse: case of family drug court

At any point in time, a patient's return to drug use can be seen either as a temporary event or as a return to persistent use. There is no formal standard for distinguishing persistent drug use from an occasional relapse. This lack of standardization persists although the consequences of either interpretation can be life altering. In a drug court or regulatory situation, for example, misinterpreting relapse as return to drug use could lead to incarceration, loss of child custody, or loss of employment. A clinician who mistakes a client's relapse for persistent drug use may fail to adjust treatment intensity to client's needs. An empirical and standardized method for distinguishing relapse from persistent drug use is needed. This paper provides a tool for clinicians and judges to distinguish relapse from persistent use based on statistical analyses of patterns of client's drug use. To accomplish this, a control chart is created for time-in-between relapses. This paper shows how a statistical limit can be calculated by examining either the client's history or other clients in the same program. If client's time-in-between relapse exceeds the statistical limit, then the client has returned to persistent use. Otherwise, the drug use is temporary. To illustrate the method, it is applied to data from three family drug courts. The approach allows the estimation of control limits based on the client's as well as the court's historical patterns. The approach also allows comparison of courts based on recovery rates.     

Antiepileptic drug evaluation in a new animal model: spontaneous petit mal epilepsy in the rat

One-third of Wistar rats bred in our laboratory present recurrent seizures whose EEG and clinical symptomatology resemble those of human petit mal. Bilateral cortical synchronous spike- and wave discharges (7-11 c/s; 200-600 microV, lasting 0.5 to 40 s) accompany behavioral arrest and are associated frequently with facial myoclonia. These seizures, observed as long as the animals survive, appear spontaneously and seem to be unrelated to surgical procedures. Antiepileptics in common clinical use were tested. Ethosuximide (greater than 12.5 mg/kg), diazepam (greater than 0.5 mg/kg), trimethadione and sodium valproate (greater than 50 mg/kg) suppressed these discharges in a dose related manner. Carbamazepine and phenytoin were ineffective or aggravated the seizures. Phenobarbital, effective at 2.5 to 10 mg/kg, was ineffective at 20 mg/kg. The similar effects of these antiepileptics on both the rats' seizures and human petit mal confirm the hypothesis that this phenomenon constitutes a valid pharmacological model of petit mal epilepsy. Its predictive value appears to be superior to that of other currently used models.     

在药物安全性评价中组织学技术流程的探讨

药物安全性评价中毒性病理学评价是最重要的一个步骤,而毒性病理学评价作为药物安全性评价体系中重要的一环,用以确定损伤靶器官、靶组织的形态及程度变化,评价受试药物是否具有毒性并判断其能否推向临床的重要指标。对组织学技术进行质量控制与评估则是确保毒性病理诊断准确性及一致性的重要前提。该文对组织学技术流程进行叙述并探讨流程中相关影响因素。     

Patent issues in drug development: Perspectives of a pharmaceutical scientist-attorney

The major purpose of this article is to emphasize the need for pharmaceutical scientists to have a better understanding of patent fundamentals. This need is illustrated by analyses of key scientific and legal issues that arose during recent patent infringement cases involving Prozac, Prilosec, and Buspar. Economic incentives for drug discovery and development clash with societal needs for low-cost pharmaceuticals in the United States and all over the world. The Hatch-Waxman Act of 1984 was enacted to promote public health by balancing the interests of brand name and generic companies. Patent protection, which provides a monopoly for a limited time, is aimed to provide such incentives. Creation of patents requires the interaction between scientists and lawyers, an endeavor made difficult by the differing intellectual spheres of their respective disciplines. Therefore, in the first place, a thorough understanding of patent fundamentals among pharmaceutical scientists will help them work more efficiently with patent attorneys. Second, it will enable them to appreciate the strengths and weaknesses of individual patents, which is critical in developing strategies amidst the ongoing patent tug-of-war between brand-name and generic companies.     

Hydrophilic silica aerogels as dermal drug delivery systems - Dithranol as a model drug.

A special class of porous silica materials, silica aerogels, was recently shown to be a potential candidate for oral drug delivery systems. It was demonstrated, that stability of drugs and their dissolution rate can essentially be improved through the adsorption on to these materials. In this work, drug loaded silica aerogels are firstly applied as dermal drug delivery systems. Dithranol is used as a representative drug since there is a need to enhance its dermal availability. The unstable and nearly water-insoluble drug exhibits a poor penetration. Release of dithranol from aerogels into various semi-solid formulations and its dissolution as well as the release and penetration into artificial membranes were investigated by Fourier-transform infrared attenuated total reflection (FTIR-ATR) spectroscopy. Two model membranes (one hydrophilic and one lipophilic) were applied. Several formulations were tested and the most promising one was used in order to study the penetration of dithranol into human stratum corneum (SC). Dithranol adsorbed on hydrophilic silica aerogels exhibited superior penetration behaviour compared to that of the standard ointment (dithranol in white soft paraffin).