PubMed Health⌕ Search

Biomedical subjects

M L Kleinberg

Publications and source records attributed to M L Kleinberg.

16 recordsLinked to original sources
PubMed1995

New approaches and technologies in drug design and discovery.

Traditional and novel approaches to drug design and screening techniques and strategies are described, and the potential benefits of new technologies are discussed. Sophisticated new approaches and technologies in the discovery and design of new drugs are replacing the traditional methods. Rational or structure-based methods of drug design and discovery that integrate techniques of x-ray crystallography, computational chemistry, and nuclear magnetic resonance spectroscopy are becoming the predominant methods. New technologies and methods for drug screening may yield significant savings in time and money, as well as increased diversity and specificity of lead compounds. Intense research activity is now being focused on small-molecule structure-based drug design, in which drugs would mimic the complex molecular interactions of natural proteins. The new approaches and technologies hold promise for dramatic therapeutic advances, particularly in the areas of transcriptionally active drugs and gene therapy. Rapid advances in drug design and screening, brought about through new technologies, may yield significant therapeutic advances and cost-effective therapies.

Biological Products↗
PubMed1990

Stability of morphine sulfate in infusion devices and containers for intravenous administration.

The stability of morphine sulfate in one brand of polyvinyl chloride (PVC) container, one brand of glass syringe, and two brands of disposable infusion devices was determined. Solutions of morphine sulfate 2 and 15 mg/mL were used to fill the PVC containers and drug administration devices. Stability was determined for both concentrations of morphine sulfate at room temperature (23-25 degrees C) and 4 degrees C in the PVC containers, glass syringes, and disposable infusion devices; stability was also determined at 31 degrees C in the disposable infusion devices. At 0, 1, 2, 4, 7, 12, and 15 days, portions of the solutions were removed and assayed in triplicate by a stability-indicating high-performance liquid chromatographic method. At each time point the drug-infusion fluid combinations were inspected visually for color changes and the presence of particulate matter, and pH was measured. Morphine sulfate 2 and 15 mg/mL remained stable for at least 12 days in all the containers and devices at each temperature tested. No substantial changes in the pH or physical appearance of the solutions were observed. Morphine sulfate can be repackaged in the disposable glass syringe, PVC container, and both disposable infusion devices for routine clinical use.

Chromatography, High Pressure Liquid↗
PubMed1990

Stability of heroin hydrochloride in infusion devices and containers for intravenous administration.

The stability of heroin hydrochloride in various drug-administration devices was studied. Heroin hydrochloride was supplied as the bulk powder by the National Institute on Drug Abuse and in the formulated dosage form by Evans Medical, Ltd. Stability was determined at concentrations of 1 and 20 mg/mL at room temperature (23-25 degrees C) and at 4 degrees C in a polyvinyl chloride (PVC) bag, a disposable glass syringe, and two disposable infusion devices. Studies at both concentrations also were conducted at 31 degrees C in the disposable infusion devices. All experiments were conducted in triplicate. A validated, stability-indicating, high-performance liquid chromatography assay was used. Heroin hydrochloride remained stable for a minimum of 15 days in the PVC bag and the Infusor infusion device at the tested temperatures and concentrations. In the glass syringe, heroin hydrochloride was shown to be stable for a minimum of 15 days at both 1 mg/mL and 20 mg/mL if refrigerated at 4 degrees C, whereas at room temperature it was stable for a minimum of 7 days at 1 mg/mL and for 12 days at 20 mg/mL. In the Intermate 200 infusion device, heroin hydrochloride was stable for a minimum of 15 days at both concentrations and all temperatures except for the 1 mg/mL concentration at 31 degrees C. In the latter case, stability was for a minimum of two days. No substantial changes in physical appearance or pH were observed in any of the containers under the conditions studied. Heroin hydrochloride can be repackaged in the disposable glass syringe, PVC bag, and each of the disposable infusion devices for routine clinical use.

Chromatography, High Pressure Liquid↗
PubMed1988

Bibliography: handling considerations for cancer chemotherapeutic agents.

Since the introduction of antineoplastic agents in the 1940s, there have been reports of the effects of these agents on workers who have had prolonged contact with them. The Regional Oncology Drug Information Center (RODIC) at Memorial Sloan-Kettering Cancer Center receives numerous inquiries nationwide regarding our policies and procedures for handling antineoplastic agents. In August 1987, RODIC conducted a computerized literature search on the handling of antineoplastic agents and the risks to hospital employees, coming in contact with these agents. We used the MEDLINE system from 1966 to the present, limiting the search to English-language articles. This article provides a comprehensive bibliography on the handling of antineoplastic agents.

Antineoplastic Agents↗
PubMed1988

Economics of providing antineoplastic drugs in a manufacturer-mixed bulk package.

The cost impact of converting from a hospital-mixed (HM) system for preparing antineoplastic-drug doses to a manufacturer-mixed bulk package (MMBP) system in a 565-bed comprehensive cancer center is analyzed. The cost per dose for nine antineoplastic agents--bleomycin, cisplatin, cyclophosphamide, doxorubicin, fluorouracil, methotrexate, mitomycin, vinblastine, and vincristine--was assessed for each system. The average dose for each drug was determined by reviewing nearly 2200 physician orders collected over nine days. Cost per dose was calculated by allocating the costs associated with the production of multiple-dose containers and withdrawal of a single dose. A time-and-motion study using standard industrial engineering methodology measured labor times for all tasks associated with the production of drug doses. Calculated costs included direct labor, drug expense, supply expense, drug waste, waste removal, overhead, management labor, and inventory reduction. Operating costs (labor, supplies, overhead, and waste and waste removal) were reduced by an average of 26% per dose for all drugs, using the MMBP system. This institution produces a high volume of antineoplastic admixtures; thus, the impact on operating costs is likely to be different in other institutions. The total measured operating and drug acquisition costs decreased for three drugs, marginally increased for five drugs, and increased substantially for one drug. Based on this institution's use of the nine antineoplastic agents, the total first-year savings from conversion from the HM system to the MMBP system would be $31,219, including a one-time inventory reduction of $94,621. However, in subsequent years, use of the MMBP system would result in increased costs of $63,402.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1981

Water permeation through polyvinyl chloride bags without overwrap.

Water loss by permeation from polyvinyl chloride i.v. containers (Viaflex, Travenol Laboratories) without an overwrap is reported. Viaflex bags without the overwrap containing 0.9% sodium chloride injection or 5% dextrose injection in 50-ml, 100-ml, 500-ml, and 1000-ml sizes were used. All sizes were stored at room temperatures (25 degrees C) and in a refrigerator (4-8 degrees C); the two smaller sizes were additionally in a frost-free freezer (-20 degrees C) and in a non-frost-free freezer (-20 degrees C). Ten bags of each type were stored for 84 days; each container weighed on days 0, 7, 14, 21, 28, 42, 56, 70, and 84 days. Based on the weight change exhibited during this initial period, the time required to lose 10% of the weight was predicted. The bags were stored for that period of time and then weighed. The weight loss exhibited zero-order kinetics. At room temperature, the 50-ml containers of both solutions lost greater than 10% during the 84-day period. During this time, the 100-ml containers of both solutions lost 9% of their weight. Weight loss in the larger sizes was less than 5% during the 84-day period at room temperature. Under the colder storage conditions, weight loss averaged much less than 5% for all sizes during the 84 days. During extended storage, weight loss continued at the same rate for the 100-ml container but was slower for the larger sizes. The Viaflex container without the overwrap may be stored in a refrigerator or freezer for up to 84 days without substantial loss of water by permeation.

Drug Packaging↗
PubMed1981

Airborne drug levels in a laminar-flow hood.

The airborne levels of fluorouracil and cefazolin sodium injections after manipulation of these drug products inside a horizontal laminar-flow hood were measured. The Biotest RCS Centrifugal Air Sampler, generally used to measure microbial levels in air, was adapted with a paper filter to measure drug levels in air. In each of nine trials, five ampuls of fluorouracil were opened in the hood and transferred to empty vials. Likewise, in each of nine trials, 50 vials of cefazolin sodium 1 g were reconstituted and transferred to small-volume i.v. solutions. Drug manipulations were performed between the hood's filter and the Biotest, which was placed inside the hood. Drug collected on the filter in the Biotest was assayed with ultraviolet spectrophotometry after extraction. The range of fluorouracil collected by the Biotest was from 0 to 14 microgram, corresponding to 0-0.07 microgram/liter of sample air. Recovered cefazolin sodium ranged from 28 to 131 microgram, or 0.02-0.11 microgram/liter of sampled air. Following routine manipulation of drug products in a laminar-flow hood, the drug can contaminate, the air flowing over the product.

Air Pollutants↗
PubMed1980

Stability of cefazolin sodium admixtures in plastic bags after thawing by microwave radiation.

The effect on antibiotic stability of thawing, with microwave radiation, cefazolin sodium admixtures frozen in polyvinyl chloride minibags was studied. Two brands of cefazolin sodium (Ancef and Kefzol) were reconstituted and placed in 50-, 100- and 250-ml polyvinyl chloride minibags of 5% dextrose in water or 0.9% sodium chloride. The resulting solutions were assayed for antibiotic stability, using an agar disk diffusion technique, and for pH. The solutions were then stored at -20 degrees C for 48 hours, thawed to room temperature in a microwave oven, and kept at room temperature for four hours, after which they were reassayed for potency and pH. The results indicated that after the freeze-thaw process, the cefazolin sodium minibag admixtures retained at least 90% of their initial antimicrobial activity. The minimal pH changes could not be related to changes in antimicrobial activity, and no color changes could be detected visually. Using a microwave oven can greatly reduce thawing time of antibiotic admixtures. To maintain solution stability and prevent accidents, it is important to calibrate the oven, avoid solution overheating, and observe full precautions in oven operation.

Biological Assay↗
PubMed1980

Effect of ascorbic acid on urine pH in patients with injured spinal cords.

The ability of ascorbic acid to lower urinary pH in patients with spinal cord injury and neurogenic bladder was studied. Ascorbic acid (1 g four times daily) or placebo was administered for five days in a double-blind, crossover study to 20 patients with spinal cord injury and neurogenic bladder. Urine pH was measured for two days before and during administration of placebo or ascorbic acid. The mean decrease in urinary pH with ascorbic acid was 0.58, but this reduction was not statistically or clinically significant. Only 7 of 20 patients showed a mean urine pH of 5.5 or less (acidic) during treatment with ascorbic acid. The study suggests that an ascorbic acid dosage of 1 g four times daily should not be used to maintain an acidic urinary pH for control of urinary tract infections in patients with spinal cord injuries.

Adolescent↗
PubMed1980

Effect of microwave radiation on redissolving precipitated matter in fluorouracil injection.

The effect on the stability of fluorouracil injection of using microwave radiation to redissolve precipitated matter was studied. Fifteen ampuls each of Fluorouracil Injection, USP, containing precipitate were heated to 60 degrees C in a microwave oven and water bath, respectively. The contents of each heated ampul and of 15 control ampuls (unheated, no precipitate) were assayed by high-performance liquid chromatography, and the pH value of each sample was measured. Each test group fell within USP concentration requirements and showed no significant decrease in potency. Among the microwave-heated ampuls, a mean drop of 0.03 pH units was significant (p less than 0.05) but did not affect drug stability or solubility, since all samples remained within the USP pH range of 8.6-9.0. Precipitated matter in fluorouracil injection can be redissolved by heating with microwave radiation without significantly affecting the drug's stability.

Chemical Precipitation↗
PubMed1980

Stability of five liquid drug products after unit dose repackaging.

The room temperature stabilities of repackaged pentazocine hydrochloride injection, promethazine hydrochloride injection, haloperidol oral concentrate, phenytoin oral suspension, and isoetharine inhalation solution were determined. After being repackaged as unit doses in a Hy-Pod Hypodermic Syringe, Ped-Pod Oral Dispenser, or NebuJect Nebulizer Injector (all made by MPL, Inc., SoloPak Division), several containers of each drug were stored at room temperature. Isoetharine samples were assayed after 15 and 30 days, while samples of the other drugs were assayed after 90, 180, and 360 days. Also, separate samples of pentazocine and promethazine were stored at 40, 50, and 60 degrees C and were assayed after 15, 30, and 90 days. The long-range stabilities of the drugs stored at elevated temperatures were predicted using the Arrhenius technique. The results indicate that, under the conditions tested, isoetharine can be stored for at least 30 days at room temperature and promethazine, pentazocine, haloperidol, and phenytoin can be stored for at least a year, all with less than 10% loss in potency. Arrhenius data indicate that pentazocine injection probably would be stable at room temperature for much longer than the 360 days for which it was tested.

Drug Packaging↗
PubMed1980

Stability of antibiotics frozen and stored in disposable hypodermic syringes.

The effect of freezing on the stability of several reconstituted antibiotics packaged in disposable hypodermic syringes was studied. The following drugs were reconstituted and, after taking samples for initial assay, were frozen at -20 degrees C in Hy-Pod hypodermic syringes: cephalothin, 1 g/5 ml; cefazolin (with water), 1 g/3 ml; cefazolin (with lidocaine injection), 1 g/3 ml; cefamandole, 1 g/3.5 ml; and nafcillin, 1 g/4 ml. At three, six, and nine months, samples of the frozen solutions were allowed to thaw at room temperature and then were assayed microbiologically. All antibiotics maintained at least 90% potency at the end of nine months. Cefazolin with lidocaine, however, turned cloudy after thawing. The data suggest that cephalothin, cefazolin with water, cefamandole, and nafcillin, when frozen and stored at -20 degrees C in Hy-Pod hypodermic syringes, may be used within nine months of initial freezing.

Anti-Bacterial Agents↗