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Improving medication use for older adults: an integrated research agenda.

Effective health care is a core determinant of successful aging, and medications are one of the most important therapeutic tools of health care providers. Most older adults use at least one prescription drug. Costs for these drugs are a substantial out-of-pocket expense for Medicare beneficiaries, and low-income older adults must weigh these costs against those of other basic needs. Although medications bring welcome relief to millions of elderly persons with age-related conditions, adverse drug events are an important cause of illness and death in these patients. Thus, the appropriate, cost-effective use of medication is central to successful aging. Despite increasing attention to geriatric pharmacotherapy, there is an enormous need for additional research to improve the use of medications among older adults. The necessary research agenda encompasses much more than just the discovery of new drugs; better use of the current pharmacopeia has great potential to improve the lives of older adults. We review four domains of pharmaceutical research: drug discovery and delivery, drug efficacy and safety, pharmacoepidemiology and drug policy, and improved access to and use of drugs. These domains encompass both the pre- and postmarketing phases of drug research. Premarketing research currently has greater magnitude and a better infrastructure than postmarketing research, yet issues arising in the two phases of research are equally important to the health and safety of older adults. A national, federally supported pharmaceutical database could greatly enhance the infrastructure of postmarketing research. However, many major improvements in medication use among older adults will also depend on closing the gap between knowledge and practice and increasing the ability of older adults to manage their medications.

Aged↗

Comparative quality tests of two types of sustained release preparation of isosorbide dinitrate.

Two commercial sustained release preparations of isosorbide dinitrate (ISDN), capsules (preparation A) and tablets (preparation B), were tested for content uniformity and dissolution pattern. The deviations in contents of the single doses from the declared content ranged from -7.7% to +9.7% which conformed to the standard (+/- 15%) of the Japanese Pharmacopeia X (JP X). Dissolution tests were performed using the rotating basket method described in JP X. The dissolution medium were No. 1 and 2 solutions (pH 1.2 and 6.8, respectively) specified in JP X disintegration test, and 0.05 M phosphate buffer solutions (pH 3.0 and 5.0). The dissolution patterns of both preparations were independent on the pH of the medium. However, there was a marked difference between the dissolution rates of the two: after 8 hr of the test, the rates of preparation A were 85-89%, but those of preparation B were only 42-50%. From preparation A a somewhat constant release of ISDN continued until the 6 hr. ISDN was determined by the HPLC method.

Capsules↗

[Failure of anti-symptomatic vaccination and the methods of vaccine activity control].

Blackleg (Clostridium chauvoei) infection in Charollais cattle appears to have undergone some etiological and pathogenic changes which are reflected in the apparent failure of vaccination. Two methods have been used to determine the quality of the vaccines in order to meet the different requirements specified by pharmacopeias. The two methods differ in the vaccination schedules of the guinea pigs and the test strain used which may be either a virulent culture or a suspension of spore in calcium chloride. Both methods appear to be efficient in selecting vaccines which provide good protection. It follows, therefore, that the vaccination failures would appear to be the result of intensive selection of beef cattle with reduced immunological response. If this is the case, the remedy for these vaccination failures might lie in an adaptation of the vaccination schedule to the early developing breeds of cattle obtained by intensive selective breeding.

Animals↗

[Continuous cervical epidural with ropivacaine in carotid surgery. Description of a case].

In the light of the recent addition of ropivacaine as a local anesthetic to our pharmacopeia, its effects at the cervical level are examined. A patient undergoing TEAC was given continuous epidural anesthesia with ropivacaine 0.5% (total dose: 167.5 mg in three hours) at C6-C7. No supplementary i.v. anesthetic was administered intraoperatively. The results obtained were compared with those of a similar case as to type of pathology and anesthetic technique, who was anesthetised with bupivacaine 0.375% (total dose: 112.5 mg in three hours-continuous epidural anesthesia) + fentanyl (0.18 mg), supplemented intravenously with ketoprophene (200 mg) + fentanyl (0.15 mg) for analgesic reasons. From this comparison, ropivacaine 0.5% was found to have greater anesthetic potential than bupivacaine 0.375%. However, it did not appear that ropivacaine exerted a protective effect on cardiovascular conditions in the course of carotid surgery. Further anesthesiologic experiences are needed to define the validity of ropivacaine in cervical surgery.

Aged↗

Antineoplastic agents: comparing off-label uses among authoritative drug compendia.

Unlabeled indications for antineoplastic drugs listed in the American Hospital Formulary-Drug Information, United States Pharmacopeia Dispensing Information-Drug Information for the Health Care Professional (Volume 1), and the American Medical Association-Drug Evaluations were evaluated. Specifically, the total number of unlabeled and unique uses (ie, not listed in either of the other two compendia) of 35 antineoplastic drugs were compared. Using a nonparametric analysis of variance to evaluate the results, significant differences in both the average unlabeled indications per drug and unique unlabeled indications per drug were found among the resources checked. The implications of the study results on reimbursement by private insurance carriers of unlabeled antineoplastic drug use is discussed in this article.

Antineoplastic Agents↗

Remarks on the investigation of sodium nucleinate by means of the limulus amebocyte lysate test.

Results of investigations of sodium nucleinate by means of the limulus amebocyte lysate (LAL) test are described. It was found that the sensitivity of this new pyrogen test to bacterial lipopolysaccharides is nearly the same as to sodium nucleinate, which is prescribed as pyrogen standard in the Pharmacopeia of the German Democratic Republic and recommended as such in the Compendium Medicamentorum.

Animals↗

[Administration of moclobemide++ in children with attention deficit hyperactivity disorder ].

ADHD is a frequent disorder that occurs among approximately 5-10% of school children. Treating this syndrome, pharmacotherapy with different forms of psychotherapy are applied. In many European countries and in the USA the primary medicines are the psychostymulative ones; in Poland, however, they are not registered in the Pharmacopeia. Thus, what seems to be important is seeking other drugs that can be useful in ADHD treatment. In the Child and Adolescent Psychiatry Clinic in Poznań, a group of 15 children (13 boys, 2 girls) at the age of 6-13 were recognised to have ADHD; they were administered moclobemid (Aurorix) in dose of 75-225 mg/d throughout the period of 8 weeks. The medicine efficacy was being estimated with psychometric, questionnaire, and experimental methods. After 4 weeks, the drug ceased to be administered to two children due to complete lack of improvement or deterioration in functioning. It was observed that in the rest of the children their attention and hyperactivity functioning improved significantly. It is essential that the medicine was well tolerated and undesirable symptoms occurred rarely.

Adolescent↗

Review of United States requirements for residual moisture in drugs.

Officially recognized procedures for residual moisture determinations on biological products are described. These include gravimetric at ambient temperature and thermogravimetric analysis at specified temperatures for specific products. The bases for selecting the optimum residual moisture for a new product are discussed and values established for currently licensed products are listed. Comparisons are made between the procedures and requirements for biological products and the water determinations specificed in U.S. Pharmacopeia XIX.

Biological Products↗

The role of the respiratory care practitioner in the evaluation of medical devices.

Health care costs continue to skyrocket, and a large portion of these costs can be attributed to technology. Some technology, such as oximetry, is relatively inexpensive compared to CAT scanning and magnetic resonance imaging. Therefore, it may elude close scrutiny and direct health care planning and, with little fanfare, drive up costs. Many of the new respiratory monitors and ventilators have not yet been subjected to the basic question: Do they affect morbidity and mortality? Technology assessment in this country is fraught with duplication of effort and complexity; the system is fragmented and in need of a strategic approach to equipment evaluation. There is meager information on cost analysis and little consensus on what needs to be done about the ethical dilemmas created by technology. Respiratory care practitioners have a significant role to play in medical device evaluation. Problem reporting of serious equipment malfunctions to the U.S. Pharmacopeia and manufacturers is essential. In-house product evaluation prior to purchase is prudent. Important feedback can be given to manufacturers through testing of prototype equipment, with the end result that our needs are met. Small departments may need to rely on information that is currently available. Laboratory and clinical research must be conducted to provide a scientific basis for the use of technology. Adequate assessment requires knowledgeable people in a position to perform the essential tasks. Respiratory care practitioners are a logical group to take an active role in the important tasks of thoroughly assessing the technologies we use.

Equipment Safety↗

Combinatorial libraries by portioning and mixing.

Combinatorial chemistry--due to its radically new synthetic methods--can be considered a forerunner of chemistry in the next century. One of the most important methods is the portioning-mixing (split-mix) synthesis which embodies the combinatorial principle. It is easily realized. Both manual and automatic devices have been described. Some features that contribute to its popularity include: it produces all possible structural combinations of the monomers, it has outstanding productivity, it leads to the formation of individual compounds in nearly equimolar quantities (affected by statistics and incomplete reactions), and it can be applied to all classes of organic compounds. Since an enormously large number of compounds can be produced in principle in a relatively short time, some practical considerations are discussed that can be useful in library design. Encoding organic libraries by peptide or nucleotide sequences or with binary tags are also described together with methods for tagging macroscopic support units with electronic chips, two dimensional bar codes or colored resin and capsule caps. Among the deconvolution strategies, the iteration method, positional scanning, omission libraries, the Selectide and the Pharmacopeia methods are mentioned. A collection of libraries prepared by portioning-mixing is also included in graphical format.

Organic Chemicals↗

Experience with vero cells at Pasteur Mérieux Connaught.

The Vero cell line has been used by Pasteur-Merieux-Connaught (PMC) since 1982 with the Cell Bank's system to produce, at the 142nd passage, inactivated polio vaccine (IPV), oral polio vaccine (OPV) and rabies vaccines. The safety of the cell line has been regularly validated at the WCB level according to the WHO and European Pharmacopeia requirements for absence of bacteria, fungi, mycoplasma and viruses. Special emphasis was devoted to establishing the absence of simian viruses (SV40, SIV, Retro-D virus, simian CMV). Reverse Transcriptase (RT) activity was also negative. At low level of passage, the Vero cells are not tumorigenic. Vaccines have been prepared in low passage level Vero cells and, together with the excellent downstream purification, has resulted in excellent safety as attested by pharmacovigilance of more than 100 million doses of IPV during 12 years, more than 20 million doses of rabies vaccine during 10 years and more than one billion of OPV during six years.

Animals↗

In vitro studies on the biochemistry and pharmacology of low molecular weight heparins.

Low molecular weight heparins (LMWHs) are obtained from unfractionated heparin by diverse chemical and enzymatic processes and findings with one LMWH cannot be extrapolated to another. Functional assays performed in vitro, evaluating antiprotease activity mediated via antithrombin III, heparin cofactor II interactions, antithrombin III binding, and plasma protein binding, showed wide variations between LMWHs, indicating that compositional differences among the LMWHs have a major impact on function. Evaluation in vitro showed varying potency in United States Pharmacopeia (USP) and anti-Xa assays. LMWHs tested at anti-Xa-adjusted concentrations exhibited varying potencies with anti-IIa, Heptest, and activated partial thromboplastin time (APTT) assays. Evaluation of these assays showed differences between LMWHs and a link with molecular weight. Each LMWH also varied in the in vitro neutralization by platelet factor 4, thrombin, and heparinase. LMWHs also varied in platelet interactions as assessed by whole blood clotting, thromboelastography and P-selectin expression, and in tissue factor pathway inhibitor release in cell culture. It was concluded that compositional variations in LMWHs give each product a unique biochemical profile. This profile, plus varying endogenous interactions and pharmacokinetic profiles may give rise to the clinical differences observed with LMWHs in specific indications.

Animals↗

Evaluation of current compendial physiochemical test procedures for pharmaceutical elastomeric closures and development of an improved HPLC procedure.

The interaction between elastomeric container closures and the solutions they confine presents a potential hazard to the consumer due to extraction of closure ingredients into the dosage form. Each of the major Pharmacopeias, the United States, the European, and the Japanese, prescribe testing procedures for elastomeric closures. These consist of a series of non-specific wet chemical analyses performed on samples extracted into water or, in some cases, isopropanol (IPA) or the drug product vehicle. No consideration is given to the extracting potential of the drug product. Results from our testing on ten randomly selected closure samples indicated that these tests are not sensitive or specific enough to accurately measure the levels of extractables. Therefore, an HPLC gradient method was developed which had the required sensitivity and specificity. The prescribed compendial extractions, when performed on the various stopper types, proved inefficient and experiments were conducted in an attempt to improve them. These included increasing the time of the extractions, increasing the closure surface area, and increasing the strength of the extracting solvent (methylene chloride). The HPLC gradient method and the compendial wet chemical tests were then used to evaluate the stopper extractables. Results of the compendial analyses on the prescribed aqueous extractions were inconclusive as the number and relative amount of extractables in the closure could not be measured. The results of the compendial testing were only marginally improved using the stronger extraction conditions. Testing was dramatically improved, however, using the HPLC gradient method. As many as twenty extractables were detected in some of the samples and, unlike the compendial analysis, low level extractables were detected in the water samples. Identification of some of the extractables was accomplished via GC/MS.

Chemical Phenomena↗

A clinical study of the effect of pellicle on the degradation of 10% carbamide peroxide within the first hour.

OBJECTIVE: The purpose of this study was to determine the degradation of 10% carbamide peroxide within the first hour of use and the effect of pellicle on the degradation of carbamide peroxide in vivo. METHOD AND MATERIALS: Fifteen subjects were assigned to wear nightguard trays filled with bleaching gel for 0.5, 2.5, 5.0, 10.0, 20.0, 40.0, and 60.0 minutes under 2 conditions: (1) subjects did not receive a prophylaxis before each bleaching treatment (pellicle was assumed to be present on the tooth surface); and (2) subjects received prophylaxis to remove pellicle from the tooth surface. At each evaluation time, 3 types of sample were collected: (1) a "grab sample," a sample of gel taken with a spatula from the reservoir of the tray on the maxillary right central incisor; (2) the remaining gel from the tray; and (3) the remaining gel scraped from the teeth. The collected gel samples were analyzed for the amount of peroxide using the United States Pharmacopeia-accepted method. Subjects were asked not to swallow the saliva during treatment but to expectorate into a beaker. The collected saliva was analyzed to determine the amount of peroxide. This sample represented the approximate amount of peroxide that subject would ingest during treatment. RESULTS: Pellicle did not affect the degradation of carbamide peroxide for the teeth or grab samples. The degradation of carbamide peroxide was exponential, except during the first 5 minutes, when the degradation rate was much higher. The saliva collected from subjects during use of the bleaching tray revealed an average of 2.1 mg of carbamide peroxide for 1 hour of bleaching treatment. CONCLUSION: The degradation rate is not affected by the removal of the pellicle.

Analysis of Variance↗

Combining a positive expiratory pressure device with a metered-dose inhaler reservoir system using chlorofluorocarbon albuterol and hydrofluoroalkane albuterol: effect on dose and particle size distributions.

BACKGROUND: Combining a positive expiratory pressure (PEP) device with inhalation of albuterol via metered dose inhaler (MDI) may improve drug delivery to the lung, but may also affect dose availability. PURPOSE: Determine the effect of interposing a PEP device on dose availability of albuterol via MDI and reservoir with either a chlorofluorocarbon (CFC) or hydrofluoroalkane (HFA) propellant. METHODS: MDI dose availability of CFC albuterol (Proventil) and HFA albuterol (Proventil HFA) using an Aerosol Cloud Enhancer (ACE) reservoir with and without a PEP device (TheraPEP) attached was determined. Drug availability was assessed using an Andersen 8-stage cascade impactor operated at 28.3 +/- 0.5 L/min. The PEP device was inserted between the reverse-firing ACE and the United States Pharmacopeia induction throat. Drug collected on impactor plates was analyzed spectrophotometrically at 276 nm, and the fine particle fraction was determined as the mass of drug < 4.7 microns. RESULTS: With CFC albuterol, total dose and drug mass < 4.7 microns (means and standard deviations) for the MDI-ACE alone were 44.4 +/- 7.7 micrograms and 33.4 +/- 2.2 micrograms, respectively, and for the MDI-ACE with TheraPEP were 50.1 +/- 6.4 micrograms and 39.8 +/- 14.3 micrograms, respectively. With HFA-albuterol sulfate, total drug and drug mass < 4.7 microns for the MDI-ACE alone, expressed as base drug, were 41.7 +/- 4.2 micrograms and 35.2 +/- 6.3 micrograms, respectively, and for the MDI-ACE with TheraPEP were 48.9 +/- 8.0 micrograms and 44.2 +/- 6.2 micrograms, respectively. There was no significant difference in dose availability between the MDI-ACE alone and with the PEP device attached (Wilcoxon signed-rank test, p > 0.05), for either CFC or HFA albuterol. CONCLUSION: Interposing the TheraPEP device at the MDI-ACE outlet does not change total dose, drug mass < 4.7 microns, or mass median aerodynamic diameter of MDI albuterol, with either CFC or HFA propellants.

Administration, Inhalation↗

Comparative dissolution testing of paracetamol commercial tablet dosage forms.

Dissolution can best be described as a tool that can provide valuable information about the availability of a drug product. In this study, nine different paracetamol tablet dosage forms available on the Turkish Drug Market have been investigated and physical controls were realized. Paddle and rotating basket apparatus methods were applied to all the formulations. In order to evaluate the dissolution rates, five different kinetics have been studied and the best fitting kinetics was found to be the Hixson-Crowell kinetics. It was found that all the preparations are in accordance with the Pharmacopeia standards.

Acetaminophen↗

[Optimization of technical parameters for processing radix Aconiti coreani].

Based on the determination of guanfu A, hypaconitine, and total alkaloids, along with the experiment of acute toxicity of sliced Radix Aconiti Coreani and in compliance with the quality standard stipulated in pharmacopeia-surface features cross section colour and odor of sliced Radix Aconiti Co-reani the technology of processing Radix Aconiti Coreani has been optimized to be steaming the drug for four hours.

Aconitine↗

Dissolution properties of different designed and formulated salbutamol tablet dosage forms.

Pharmaceutical availability or in vitro availability is one of the aspects of drug bioavailability. Dissolution can be described best as a tool that can provide valuable information about the availability of a drug product. Dissolution test was performed on three different designed and formulated of salbutamol tablet formulations marketed in Turkey. The test methods were the paddle method and the rotating basket method described in United States Pharmacopeia. All studied formulations showed a good agreement with pharmacopeial requirements. In particular all studied commercial tablet formulations showed a quite fast release of the antiasthmatic drug. Other type of table formulations showed slow release. In order to evaluate the dissolution rates five different kinetics have been examined and the best fitting kinetics was found to be RRSBW kinetic.

Albuterol↗