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Biomedical subjects

L V Allen

Publications and source records attributed to L V Allen.

At least 55 records · Page 3Linked to original sources
PubMed1989

Pharmacokinetics of trimethoprim in the rat.

The pharmacokinetics of trimethoprim was studied in male Sprague-Dawley rats following the intravenous administration of trimethoprim at a dose of 25 mg/kg. Plasma and tissue levels of trimethoprim, as a function of time, were determined by reversed-phase high-performance liquid chromatography. The disposition of trimethoprim was described by both a two-compartment open model with elimination from a central compartment and a noncompartmental method. For the compartmental analysis, the terminal elimination rate constant, elimination half-life, apparent volume of distribution in the central compartment, apparent volume of distribution in the central compartment based on the area under the plasma concentration-time curve, and volume of distribution at steady state, were determined to be 0.007 min-1, 99 min, 2059 mL/kg, 5729 mL/kg, and 2473 mL/kg, respectively. Noncompartmental pharmacokinetic parameters were obtained by the statistical moment theory. The estimates for mean residence time, clearance, and volume of distribution at steady state of trimethoprim were calculated to be 52 min, 40 mL.min-1kg-1, and 2097 mL, respectively. Tissue distribution of trimethoprim followed a biphasic phenomenon with a maximum concentration at 30 min for heart, lung, spleen, liver, kidney, seminal vesicles, and muscle, and at 45 min for testicles, 20 min for prostate gland, and less than 10 min for brain. The data show that compared with the plasma concentration, higher levels of trimethoprim were found in heart, lung, spleen, liver, kidney, prostate gland, and seminal vesicles; a similar concentration was found for muscle, but lower levels of trimethoprim were found for brain and testicles.

Animals↗
PubMed1989

Stability of cefazolin sodium, cefoxitin sodium, ceftazidime, and penicillin G sodium in portable pump reservoirs.

The stability of cefazolin sodium, cefoxitin sodium, ceftazidime, and penicillin G sodium in prefilled drug reservoirs that were stored at -20 degrees C for 30 days, thawed at 5 degrees C for four days, and pumped at 37 degrees C for one day was studied. Each antimicrobial agent was diluted with sterile water for injection to a concentration representative of the most common dosage when administered via a portable infusion pump. Ten milliliters of each drug solution was placed in individual glass vials to serve as controls, and volumes appropriate to deliver the designated dosages were loaded into the drug reservoirs. Triplicate reservoirs were prepared for each drug. One-milliliter samples from all containers were taken on days 0, 30, 31, 32, 33, 34, 34.5, and 35. All solutions were observed for color change and precipitation. Drug concentrations were determined using high-performance liquid chromatography. Leaching of the plasticizer diethylhexyl phthalate (DEHP) was analyzed by packed-column gas chromatography on days 0 and 35. No color change or precipitation was observed. No DEHP concentrations above 1 ppm were detected. More than 90% of the initial concentrations of each drug remained, except penicillin G sodium, which had a mean concentration of 83.9 +/- 0.5% at the end of the study. Cefazolin sodium, cefoxitin sodium, and ceftazidime in admixtures with sterile water for injection are stable under the conditions of this study. Penicillin G sodium should not be administered for more than 12 hours after such a cycle of freezing and thawing.

Cefazolin↗
PubMed1989

Stability of a nonaqueous trimethoprim preparation.

A nonaqueous formulation of trimethoprim for injection was prepared, and the stability of the undiluted solution (50 mg/mL) was studied. Six nonaqueous injectable solvents were used in an attempt to attain a trimethoprim concentration of 50 mg/mL; N,N-dimethylacetamide was found suitable, and a cosolvent system containing 52% N,N-dimethylacetamide and 48% propylene glycol was developed. The stability of trimethoprim 50 mg/mL in this solution after storage at temperatures of 80 degrees C, 90 degrees C, and 140 degrees C was studied using high-performance liquid chromatography. Samples were also examined visually for signs of color change or precipitation. More than 90% of the initial concentration remained after storage at 80 degrees C for 45 days. Examination of the stability data suggested that trimethoprim degradation was a zero-order process, although a first-order process could not be excluded. Extrapolation of data from an Arrhenius plot yielded a zero-order trimethoprim degradation rate constant at 25 degrees C of 0.0113% day-1. The time for 10% trimethoprim degradation at 25 degrees C would be 885 days. No precipitation was observed, but the initially colorless solution turned yellow or brown during storage. The extent of color change was associated with the degree of trimethoprim degradation. Trimethoprim, when prepared in the nonaqueous solution described, is stable at 25 degrees C. The preparation may be suitable for intravenous use.

Acetamides↗
PubMed1989

Stability of morphine sulfate in portable pump reservoirs during storage and simulated administration.

The stability of four concentrations of morphine sulfate injection in prefilled reservoirs for portable infusion pumps was studied after storage for 30 days at refrigerated and room temperature and after a three-day simulated administration period at body temperature. Thirty-milliliter samples of morphine sulfate injections in four concentrations--1, 5, 15, and 25 mg/mL--were loaded into a pump reservoir. The reservoirs were stored in the dark at 5 degrees C and 25 degrees C for 30 days. Samples were taken from each reservoir immediately after loading and after 7, 14, and 30 days of storage. The reservoirs were then connected to portable infusion pumps, which were run for three days at a flow rate of 0.4 mL/hr at 37 degrees C. The last sample was collected at the end of the three-day period. Samples were assayed for morphine sulfate content by high-performance liquid chromatography. The concentration of morphine sulfate increased up to 6% (for the 5-mg/mL sample) at refrigerated temperature and up to 16% (for the 15-mg/mL sample) at room temperature after 30 days' storage in the reservoirs. Evaporation of water from the reservoirs may have accounted for this phenomenon. No absolute relationship was found between the initial concentration of morphine sulfate and the percentage concentration increase after storage for 30 days. The change in morphine sulfate concentration before and after the three-day pumping period was not significant. Injectable solutions of morphine sulfate in concentrations ranging from 1 to 25 mg/mL are stable when stored at refrigerated temperature for 30 days in a prefilled drug reservoir.

Chromatography, High Pressure Liquid↗
PubMed1989

Stability of fluorouracil administered through four portable infusion pumps.

The stability of fluorouracil in four portable infusion pumps under simulated infusion conditions was studied. Three commercially available fluorouracil aqueous solutions (50 mg/mL) were used. Samples adjusted to six pH levels were examined for precipitate. Drug reservoirs of four different portable infusion pumps were filled with 70 mL of each fluorouracil injection. Under conditions simulating actual use, the reservoirs were attached to the pumps and the solutions were pumped at a rate of 10 mL/24 hours over a seven-day period at 25 degrees C and 37 degrees C. Samples at the distal end of the extension tubing were collected hourly for the first 10 hours and at 12-hour intervals thereafter. Visual observations and pH determinations were made immediately. Drug concentrations were determined by reverse-phase high-performance liquid chromatography. Diethylhexylphthalate (DEHP) concentrations (the result of leaching from the plastic tubing and container) were determined by gas chromatography. In the pH study, precipitate appeared immediately in all fluorouracil injections below pH 8.52; precipitate was observed after two to four hours at pH 8.60-8.68. Under simulated infusion conditions, no apparent changes in concentration or pH were detected with any of the brands of drugs or portable infusion devices. At 25 degrees C, a fine white precipitate was observed in the extension tubing of all devices with the Roche brand of fluorouracil 48 to 96 hours after the pumping cycle began. The amount of DEHP leached from the drug reservoirs over the seven-day period was less than 1 ppm at both temperatures. All tested brands of fluorouracil injection were found to be stable under simulated infusion conditions over a seven-day period at 37 degrees C.

Chemistry, Pharmaceutical↗
PubMed1988

Degradation kinetics of phentolamine hydrochloride in solution.

The degradation kinetics of phentolamine hydrochloride in aqueous solution over a pH range of 1.2 to 7.2 and its stability in propylene glycol- or polyethylene glycol 400-based solutions were investigated. The observed rate constants were shown to follow apparent first-order kinetics in all cases. The pKa determination for phentolamine hydrochloride was found to be 9.55 +/- 0.10 (n = 5) at 25 +/- 0.2 degrees C. This indicated the protonated form of phentolamine occurs in the pH range of this study. The pH-rate profile indicated a pH-independent region (pH 3.1-4.9) exists with a minimum rate around pH 2.1. The catalytic effect of acetate and phosphate buffer species is ordinary. The catalytic rate constants imposed by acetic acid, acetate ion, dihydrogen phosphate ion, and monohydrogen phosphate ion were determined to be 0.018, 0.362, 0.036, and 1.470 L mol-1 h-1, respectively. The salt effect in acetate and phosphate buffers followed the modified Debye-Huckel equation quite well. The ZAZB value obtained from the experiment closely predicts the charges of the reacting species. The apparent energy of activation was determined to be 19.72 kcal/mol for degradation of phentolamine hydrochloride in pH 3.1, 0.1 M acetate buffer solution at constant ionic strength (mu = 0.5). Irradiation with 254 nm UV light at 25 +/- 0.2 degrees C showed a ninefold increase in the degradation rate compared with the light-protected control. Propylene glycol had little or no effect on the degradation of phentolamine hydrochloride at 90 +/- 0.2 degrees C; however, polyethylene glycol 400 had a definite effect.

Buffers↗
PubMed1988

Compatibility of verapamil hydrochloride with penicillin admixtures during simulated Y-site injection.

The compatibility of verapamil hydrochloride during simulated Y-site injection with i.v. admixtures containing 11 different penicillins was studied. Admixtures of penicillin G potassium (62.5 mg/mL), nafcillin sodium (40 mg/mL), oxacillin sodium (40 mg/mL), ampicillin sodium (40 mg/mL), carbenicillin disodium (40 mg/mL), methicillin sodium (40 mg/mL), ticarcillin sodium (40 mg/mL), azlocillin sodium (40 mg/mL), mezlocillin sodium (40 mg/mL), piperacillin sodium (40 mg/mL), and amdinocillin (20 mg/mL) were prepared in both 5% dextrose injection and 0.9% sodium chloride injection in minibags. Verapamil hydrochloride injection 4 mL (10 mg) was then added to each admixture, and the admixtures were examined macroscopically and microscopically for precipitate immediately and at 15 minutes and 24 hours after mixing. To simulate Y-site injection of verapamil, verapamil hydrochloride injection 1 mL (2.5 mg) was added to 1 mL of each penicillin admixture in a test tube. For admixtures in which precipitates formed, the pH was recorded before and after verapamil was added to the admixtures. Loss of verapamil hydrochloride when mixed with the penicillin admixtures was determined using reverse-phase high-performance liquid chromatography. Addition of verapamil hydrochloride to admixtures containing nafcillin sodium, oxacillin sodium, ampicillin sodium, and mezlocillin sodium resulted in substantial loss of verapamil hydrochloride. The results for the Y-site injection study showed visible precipitation with the same penicillin admixtures. Because a precipitate formed when verapamil hydrochloride was added to nafcillin sodium, oxacillin sodium, ampicillin sodium, or mezlocillin sodium in the diluents studied, we recommended that verapamil hydrochloride be administered separately or that the i.v. tubing be flushed thoroughly before and after this drug is administered through a Y-injection site with these penicillin admixtures.

Drug Combinations↗
PubMed1988

Stability of amoxicillin trihydrate-potassium clavulanate in original containers and unit dose oral syringes.

The stability of reconstituted amoxicillin trihydrate-potassium clavulanate oral suspension both in original containers and pre-packaged in commercially available oral syringes stored at various temperatures was determined. Amoxicillin trihydrate 125 mg/5 mL-potassium clavulanate 31.25 mg/5 mL and amoxicillin trihydrate 250 mg/5 mL-potassium clavulanate 62.5 mg/5 mL were reconstituted according to the manufacturer's instructions. The reconstituted suspensions in the original containers and in five brands of oral syringes were stored at 5 degrees C and 25 degrees C and -10 degrees C, 5 degrees C, and 25 degrees C, respectively, for 0, 2, 4, 7, and 14 days. The concentrations of amoxicillin trihydrate and potassium clavulanate remaining after storage were assayed in triplicate by reverse-phase high-performance liquid chromatography, using a stability-indicating method. An F statistic was calculated to determine whether different syringe brands had significantly different effects on drug stability. Amoxicillin trihydrate was stable for at least 10 days in the original containers and all types of oral syringes at 5 degrees C. However, potassium clavulanate was stable for 11.1 days in original containers and less than 5 days in all types of oral syringes at 5 degrees C. The effect of syringe brand on the stability of drugs over time at specific storage conditions and temperature was significant for potassium clavulanate at 5 degrees C and for both amoxicillin trihydrate and potassium clavulanate at 25 degrees C. The manufacturer's guidelines for storage of reconstituted amoxicillin trihydrate-potassium clavulanate oral suspension in the original containers should not be applied to dosages repackaged in unit dose oral syringes.

Amoxicillin↗
PubMed1987

Stability of papaverine hydrochloride and phentolamine mesylate in injectable mixtures.

The stability of papaverine hydrochloride and phentolamine mesylate combined in a single vial was studied. Injectable mixtures (10 mL) of papaverine hydrochloride 300 mg and phentolamine mesylate 5 mg (from two sources) were prepared by adding the contents of one vial of lyophilized phentolamine mesylate to the contents of one vial of papaverine hydrochloride injection. The vials were stored at 5 degrees C and 25 degrees C. Duplicate aliquots of the mixtures were obtained, and the concentrations of papaverine hydrochloride and phentolamine mesylate remaining at time 0 and after 1, 2, 5, 10, 20, and 30 days were determined in triplicate by a stability-indicating high-performance liquid chromatographic assay. The concentration of papaverine hydrochloride stored in the vials remained constant (less than 1% loss) over the 30-day period at both 5 degrees C and 25 degrees C. Phentolamine mesylate was less stable than papaverine but still retained more than 97% of its original concentration after 30 days at 5 degrees C and more than 95% of its original concentration at 25 degrees C. Papaverine hydrochloride and phentolamine mesylate are stable in injectable mixtures when stored for up to 30 days at 5 degrees C or 25 degrees C.

Chromatography, High Pressure Liquid↗
PubMed1985

Compatibility of furosemide with aminoglycoside admixtures.

The compatibility of furosemide with i.v. admixtures containing each of five different aminoglycosides was studied. Admixtures of amikacin 2 mg/ml, gentamicin 1.6 mg/ml, kanamycin 2 mg/ml, netilmicin 1.5 mg/ml, and tobramycin 1.6 mg/ml (as the sulfate salts) were prepared in both 5% dextrose injection and 0.9% sodium chloride injection in minibags. Furosemide injection 4 ml (40 mg) was then added to each admixture, and the admixtures were examined visually and microscopically for precipitate. The macroscopic and microscopic evaluations were repeated 15 minutes and 24 hours after mixing. To simulate Y-site injection of furosemide, furosemide injection 1 ml (10 mg) was added to 1 ml of each aminoglycoside admixture in a syringe. For admixtures in which precipitates formed, the pH was recorded before and after adding furosemide to subsequent admixtures and also after dropwise addition of 1N sodium hydroxide until the precipitate dissolved. Precipitates were identified using spectrophotometric analysis and melting point determinations. Addition of furosemide resulted in a precipitate only in admixtures containing gentamicin sulfate or netilmicin sulfate; the results for the simulated Y-site injection study were the same. Spectrophotometric analysis and melting point determinations revealed that the precipitate was furosemide. Because furosemide precipitates when added to admixtures containing either gentamicin sulfate or netilmicin sulfate in 5% dextrose injection or 0.9% sodium chloride injection, furosemide should be administered separately or the i.v. tubing should be flushed thoroughly before and after administering this drug via a Y-injection site.

Amikacin↗
PubMed1982

Evaluation of four assay methods for determination of tobramycin in human serum.

Four assay procedures for tobramycin in serum--enzyme immunoassay (I), substrate-labeled fluorescent immunoassay (II), radioimmunoassay (III), and bioassay (IV)--were compared and evaluated by replicate and analytical recovery studies. I and II were about 50% more precise than III and IV. II was substantially more nearly accurate than the other methods and also gave the best reproducibility (correlation coefficient 0.992 between-day). The least expensive method was IV. Ease of handling favored I and II. Overall, we find II to be the most acceptable procedure for use in the clinical laboratory.

Anti-Bacterial Agents↗
PubMed1981

Effect of surfactant on tetracycline absorption across everted rat intestine.

Absorption of tetracycline hydrochloride (500 micrograms/ml) from oxygenated modified Krebs buffer in randomized everted rat jejunal segments was determined alone and in the presence of calcium, polysorbate 80, and calcium plus polysorbate 80. Surfactant increased absorption of tetracycline in the presence and absence of calcium, with 0.01% (w/v) polysorbate 80 increasing transfer to the greatest extent of the concentrations examined(0.005, 0.01, 0.05, 0.1, and 1%); tetracycline hydrochloride + 12.5 mM CaCl2, 143 +/- 45 micrograms/ml; tetracycline hydrochloride + polysorbate 80, 389 +/- 18 micrograms/ml; tetracycline hydrochloride + 12.5 mM CaCl2 + polysorbate 80, 255 +/- 31 micrograms/ml. On the premise that the effective surfactant concentration is similar to the critical micelle concentration, an absorption mechanism based on micellar solubilization is postulated.

Animals↗
PubMed1981

Specificity of the EMIT drug abuse urine assay methods.

A investigation was conducted to determine the specificity of the EMIT DAU method of drugs of abuse analysis. Drug-free urine, from healthy volunteers, was individually spiked at 1000, 100, 10, and 1 microgram/mL concentrations with each of 162 different drug substances. These spiked samples were analyzed with the EMIT DAU assay for amphetamines, barbiturates, benzodiazepine metabolites, cocaine metabolites, methadone, opiates, and propoxyphene. Although several of the test methods yielded positive results at a concentration of 100 micrograms/mL, many drugs will probably not reach that concentration in the urine. The number of drugs giving a false positive at a concentration of 100 micrograms/mL was very low. The assay for cocaine metabolites gave no false positive results at any of the concentrations studied while the assay for methadone gave the largest number of false positive results. When interpreting the results of this investigation one must consider that in many cases drug metabolites will exist in the urine, salt forms of the drugs studied were used, and ionic strength and pH effects can interfere with the lysozyme enzyme system used in the EMIT DAU assays. In summary, the proper utilization of specificity information may assist the analyst in explaining unusual values obtained in the laboratory, particularly when the subject is concurrently using prescription or nonprescription medication.

False Positive Reactions↗
PubMed1980

Oxygen solubilization in egg lecithin dispersed in distilled water and physiological electrolyte fluids.

Gaseous oxygen solubilization in egg lecithin dispersed in distilled water, saline, and a multi-ion physiological electrolyte solution was determined and compared to controls deficient in egg lecithin. Significant oxygen solubilization occurred in the presence of egg lecithin. Oxygen solubilization was significantly greater in saline and in the multi-ion physiological electrolyte solution than in distilled water.

Eggs↗
PubMed1979

Stability of oral liquid penicillins in unit dose containers at various temperatures.

The effect of freezing on the stability of reconstituted, unit dose packaged oral amoxicillin trihydrate and ampicillin suspensions and penicillin V potassium solutions was studied. Powders for suspension or solution of the three penicillins were reconstituted according to manufacturers' directions to yield a concentration of 250 mg/5 ml. Samples of 5 ml then were stored in amber, screw-cap, glass vials at 25 C, 5 C, 0 C, -10 C or -20 C for 5, 10, 20, 30 or 60 days. The concentration of active constituents remaining after storage was determined spectrophotometrically. All three penicillins retained at least 90% of their original activity for at least 60 days when stored at -20 C. Ampicillin and pencillin V potassium retained at least 90% of their activity after 60 days of storage at -10 C but amoxicillin concentration decreased to 88% and 87% of initial concentration after 60 days storage at -10 C and 0 C, respectively. Degradation appeared to be by a zero-order process for amoxicillin and ampicillin and by a first-order process for penicillin V potassium. It appears that oral solutions of amoxicillin, ampicillin and penicillin V potassium can be effectively stored for at least 50 days in a freezer at -10 C with little loss of activity.

Administration, Oral↗
PubMed1979

Sodium acetate as a preservative in protein hydrolysate solutions.

The inhibitory effect of sodium acetate on microorganism growth in protein hydrolysate solutions was studied. Solutions of 5% protein hydrolysate and 5% dextrose in water (seven parts) and 50% dextose in water (three parts) containing 0, 30, 50 and 90 mEq/liter of sodium acetate were inoculated with Staphylococcus aureus, Escherichia coli, Candida albicans and Pseudomonas aeruginosa. The number of colony-forming units in the solutions after inoculation was compared with that after incubation for 24 hours at 37 C. Sodium acetate inhibited growth of S aureus and E coli. Growth of P aeruginosa was inhibited in protein hydrolysate solutions with and without sodium acetate; inhibition could not be attributed solely to sodium acetate and may have been releated to pH of the solutions (4.7 to 5.4). Growth of C albicans was not inhibited by sodium acetate. Sodium acetate reduced growth of some common contaminants of protein hydrolysates. Sodium acetate is known to reduce metabolic acidosis, a reported complication of parenteral nutrient therapy and a possible predisposing factor in C albicans sepsis. Addition of sodium acetate to protein hydrolysate solutions should be considered seriously.

Acetates↗