Pharmaceutical applications for molecularly imprinted polymers

Molecular imprinting is a means of introducing sites of specific molecular arrangement into an otherwise uniform polymeric matrix. This is achieved by formation of a pre-polymerisation complex between complementary monomers and the template molecule. Subsequent polymerisation in the presence of a crosslinker, in a porogenic environment, results in the production of a macroporous polymer capable of specific molecular recognition. This paper considers potential roles for molecularly imprinted polymers within a pharmaceutical remit. Applications including controlled release, drug monitoring devices and biological receptor mimetics are discussed. Histamine and ephedrine molecularly imprinted polymers (MIPs) were studied as potential biological receptor mimics whilst a propranolol MIP was investigated for its use as a rate attenuating selective excipient in a transdermal controlled release device. Preliminary studies concerning the preparation of a theophylline selective transcutaneous monitoring device, using a theophylline MIP, are also described.     

Is diurnal variation in absorption of slow-release aminophylline an age-related phenomenon?

Summary To specifically assess the possible influence of ageing on the changes in theophylline absorption, the plasma concentration-time profiles of sustained-release aminophylline were studied in 8 young and 8 elderly subjects after 9 a.m. and 9 p.m. administration.After 9 p.m. administration, in elderly subjects, maximum plasma theophylline concentrations (C_max) were decreased, time to maximum concentration (t_max) was increased, and area under plasma concentration-time curve (AUC) was decreased compared to 9 a.m. dosing. This was true for single dose and at steady-state and suggests delayed and diminished absorption at night. No statistically significant changes were seen in the young subjects.This study therefore suggests that time related changes in absorption may be more significant in elderly subjects, possibly due to postural differences after 9 p.m. dosing, and this should be borne in mind when prescribing.     

Pulmonary administration of aerosolised fentanyl: pharmacokinetic analysis of systemic delivery

Aims Pulmonary drug delivery is a promising noninvasive method of systemic administration. Our aim was to determine whether a novel breath-actuated, microprocessor-controlled metered dose oral inhaler (SmartMist^TM, Aradigm Corporation) could deliver fentanyl in a way suitable for control of severe pain.
Methods Aersolised pulmonary fentanyl base 100–300  μg was administered to healthy volunteers using SmartMist^TM and the resultant plasma concentration-time data were compared with those from the same doses administered by intravenous (i.v.) injection in the same subjects.
Results Plasma concentrations from SmartMist^TM were similar to those from i.v. injection. Time-averaged bioavailability based upon nominal doses averaged 100%, and was >50% within 5  min of delivery. Fentanyl systemic pharmacokinetics were similar to those previously reported with no trends to dose-dependence from either route. Side-effects (e.g. sedation, lightheadedness) were the same from both routes.
Conclusions Fentanyl delivery using SmartMist^TM can provide analgetically relevant plasma drug concentrations. This, combined with its ease of noninvasive use and transportability, suggests a strong potential for field and domicilliary use, and for patient controlled analgesia without the need for i.v. cannulae.     

Assessment of multiply-handicapped children: A new approach and consumer reactions

Summary The assessment process for children evidencing multiple handicaps can be a lengthy and arduous task for both the child and his parents. The customary office-by-office or clinic-by-clinic sequence necessary for a thorough evaluation of the child consumes inordinate amounts of time, fosters anxiety, and frustration, in the participants, and produces, more often than not, a great body of paperwork-reports of each evaluation-but no comprehensive, integrated, treatment program. And, the responsibility for the implementation of the recommendations reported by each individual examiner is totally left to confused, anxious, and often angry parents, who have lived with and observed their child, but who have largely been omitted from this process. The Comprehensive Assessment Service of the Eleanor Roosevelt Developmental Services, New York State Department of Mental Hygiene, was designed to offer a comprehensive, high-quality, evaluation of a child and his family on a time-limited basis, to utilize the parents as participants in the process, to develop a treatment program tailored to the needs of the child and his family, and to act as “advocates” for the family regarding implementation of the program. A theme central to the development of this process is that, in working with multiply-handicapped children and their families, a multidisciplinary team approach is most necessary. On the basis of the responses of the consumers of this service, it appears that not only is this a necessary approach, it is also one that is workable and fruitful. Joseph A. Steger, Ph.D., Kansas State University, is currently a Professor of Management at Rensselaer Polytechnic Institute. His research and consulting work include clinical management, research and development management, and studies of animation and productivity in science and engineering. He also directs a program dealing with the early identification of management talent. Richard Woodhouse, Ph.D., State University of New York at Albany, is a Program Analyst with the New York State Department of Mental Hygiene. He developed and directs program evaluation for a mental health unit, and has directed the development of an automated client information system based on needs and services.     

Locomotor activity detects subunit-selective effects of agonists and decahydroisoquinoline antagonists at AMPA/kainic acid ionotropic glutamate receptors in adult rats

Rationale In vitro studies have identified a series of decahydroisoquinoline compounds with differential selectivity for the subunits that comprise AMPA/kainic acid receptors. Compounds have been identified that have preferential activity at AMPA receptors (LY302679), whereas others (LY377770) have affinity for GluR5-kainic acid preferring subunit, which is activated by ATPA and kainic acid.Objectives These studies set out to determine if locomotor activity could differentiate these profiles in vivo.Methods Locomotor activity was assessed in photocell drums in male Lister Hooded rats.Results AMPA, kainic acid and the GluR5 selective agonist ATPA, all suppressed spontaneous locomotor activity (SLA) in rats at doses of 1.0, 5.0 and 20 mg/kg resp. All three agonists achieve micromolar concentrations measured in whole brain after dosing with 10 mg/kg SC. The decahydroisoquinoline antagonist compounds, LY302679 (GluR2), LY293558 (GluR2, 5) and LY377770 (GluR5) all decreased SLA in rats (ED_min 2.5, 5.0 and 20 mg/kg respectively). The rank order of potency at GluR2 subunits (LY302679>LY293558>LY377770) was reflected in the same rank order of activity for suppression of SLA. LY293558 reversed the suppression of SLA induced by all three agonists (0.62–2.5 mg/kg). LY377770 reversed the effects of ATPA only (ED_min 1.0 mg/kg), LY302679 (ED_min 2.5 mg/kg) attenuated the effect of kainic acid but was ineffective against AMPA and ATPA.Conclusions Both agonist and antagonist suppression of SLA is associated with greater affinity for the GluR2 subunit, while compounds with affinity for the GluR5 subunit were less potent in suppressing SLA.