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Compatibility of commonly used bone marrow transplant drugs during Y-site delivery.

The Y-site compatibility of medications routinely used in bone marrow transplant patients was studied. Two methods were used to evaluate the compatibility of pairs of various i.v. drugs and nutrient fluids. In the first, the drugs were combined in a 1:1 ratio in test tubes, which were visually evaluated immediately and at 1, 4, and 24 hours under normal light and against a white background. The second method involved simulated infusion through a Y-site and a membrane filter. Filter disks were examined under 51 x magnification for precipitates. "Administration" time ranged from one minute to five hours. Most of the combinations were compatible. Exceptions (incompatibilities or inconclusive findings) were amikacin plus a total parenteral nutrient (TPN) admixture; cyclosporine plus dopamine hydrochloride, magnesium sulfate, ondansetron, a parenteral nutrient solution, the TPN admixture, or the TPN admixture with phytonadione; and heparin sodium in either 5% dextrose injection or 0.9% sodium chloride injection plus the TPN admixture or vancomycin. The two study methods were in agreement for all drug combinations except those involving cyclosporine. Cyclosporine in 0.9% sodium chloride injection yielded many fine particles on the filter disk. The combination of cyclosporine with other drugs did not appear to increase the number of particles on the disk, but the results must still be considered inconclusive. Two methods used to determine the compatibility of bone marrow transplant agents when mixed in a Y injection site yielded the same results, except for combinations involving cyclosporine. Most of the combinations were compatible.

Anti-Infective Agents↗

Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies.

We describe extensions to the method of Pritchard et al. for inferring population structure from multilocus genotype data. Most importantly, we develop methods that allow for linkage between loci. The new model accounts for the correlations between linked loci that arise in admixed populations ("admixture linkage disequilibium"). This modification has several advantages, allowing (1) detection of admixture events farther back into the past, (2) inference of the population of origin of chromosomal regions, and (3) more accurate estimates of statistical uncertainty when linked loci are used. It is also of potential use for admixture mapping. In addition, we describe a new prior model for the allele frequencies within each population, which allows identification of subtle population subdivisions that were not detectable using the existing method. We present results applying the new methods to study admixture in African-Americans, recombination in Helicobacter pylori, and drift in populations of Drosophila melanogaster. The methods are implemented in a program, structure, version 2.0, which is available at http://pritch.bsd.uchicago.edu.

Algorithms↗

Comparison of two formulas to calculate alveolar oxygen tension in canine oleic acid pulmonary edema.

Alveolar oxygen tension (PAO2) is calculated by either of two mathematical formulas incorporating various respiratory variables. The first formula, Equation 1, assumes a constant RQ of 0.8; the second formula, Equation 2, uses the mixing equation and requires analysis of inspired, mixed expired, and end-tidal gas samples. We tested the consistency of these formulas before and after asymmetric oleic acid pulmonary edema, then calculated and compared venous admixture values using the PAO2 value derived from each formula. Before oleic acid, Equations 1 and 2 were similar (213 +/- 22 vs. 211 +/- 22 [SD] torr, respectively), as were venous admixture values (8.7 +/- 2.9% vs. 8.5 +/- 2.9%, respectively). After oleic acid injury, Equation 1 was significantly lower than Equation 2, thus slightly but consistently underestimating venous admixture (29.9 +/- 12.2% vs. 30.2 +/- 12.3%; p less than .01). However, the venous admixture values obtained after oleic acid injury calculated from Equations 1 and 2 correlated closely (r2 = .998; p less than .001), and the clinical differences yielded by the two formulas would be minimal. We recommend using the simpler formula (Eq. 1) when calculating PAO2.

Animals↗

Accuracy and variability of intravenous theophylline preparations.

Numerous physiologic factors affect the disposition of theophylline. One nonpatient factor that can influence steady-state theophylline concentration is the administered dosage. The accuracy and variability of hospital pharmacy-prepared i.v. admixtures of theophylline has not been quantitated. A study was designed to evaluate variation in theophylline concentrations from two sources of theophylline admixtures--one by a hospital pharmacy i.v. room and one by a pharmaceutical manufacturer making a premade product. For the theoretical 1.6 mg/ml admixture, the mean theophylline concentration of the pharmacy-prepared solution was lower than that of premixed, whereas the absolute percent error of the premixed product was less than that of the pharmacy bags. For the theoretical 3.2 mg/ml admixture, the theophylline concentration of the premixed product was lower than that of both pharmacy products, whereas the absolute percent error of the pharmacy bags was less than that of the pharmacy bottles and premixed bags. Our data imply that variability in theophylline concentration can occur depending on the method of preparation, drug concentration, and formulation. Pharmacokinetic monitoring of theophylline should include an assessment of methods of i.v. drug preparation. Pharmacy departments should have a policy that assures consistency in the method of preparation of i.v. drugs.

Chemistry, Pharmaceutical↗

Inhibition of cytochrome P-450 attenuates hypoxemia of acute lung injury in dogs.

The intravenous administration of ethchlorvynol (ECV), in dogs, resulted in an acute lung injury (ALI) characterized by a 200 +/- 80% increase in venous admixture and a 142 +/- 30% increase in extravascular lung water (EVLW). Pretreatment with the cytochrome P-450 inhibitor 8-methoxypsoralen prevented the ECV-induced increase in venous admixture but not the increased EVLW. These findings parallel those reported for cyclooxygenase inhibition in ECV-induced ALI and suggest that an arachidonic acid (AA) metabolite of pulmonary cytochrome P-450 activity may mediate the increase in venous admixture of ALI. We demonstrate that canine pulmonary microsomes metabolize [1-(14)C]AA to a variety of products, including the cytochrome P-450 metabolites 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid (EET). In prostaglandin F2 alpha-contracted, isolated pulmonary venous rings, 5,6-EET induced relaxation in a concentration-dependent manner. This action of 5,6-EET was prevented by indomethacin (10(-5) M). These results suggest that may serve as the cyclooxygenase-dependent endogenous pulmonary vasodilator responsible for the increase in venous admixture of ECV-induced ALI.

8,11,14-Eicosatrienoic Acid↗

Stability of fat-soluble vitamins A (retinol palmitate), E (tocopherol acetate), and K1 (phylloquinone) in total parenteral nutrition at home.

Our purpose was to extend previous studies of the stability of vitamins A (retinol palmitate), E (tocopherol acetate), and K1 (phylloquinone) to total parenteral nutrition at-home (TPNH) admixtures. First, stability over 20 days was tested. Experimental conditions included presence or absence of lipids, presence or absence of trace elements, and storage in a glass bottle or in a single or multi-layer plastic bag (ethylene vinyl acetate, polyvinyl chloride, Stedim 5, and Stedim 6). The 20-day storage studies were conducted at 4 degrees C or at ambient air temperature. The second part of the study consisted of exposing to natural light TPNH admixtures with or without lipids, but with trace elements, in the same containers (except polyvinyl chloride). Finally, a clinical situation of TPNH was simulated with a TPNH admixture prepared 11 days before the test in a Stedim 6 plastic bag and stored at 4 degrees C in total darkness. For vitamins A, E, and K1, we observed good stability for 20 days; the final concentrations ranged from 75% to 100% of initial concentrations whatever the conditions studied. It appears that there is no significant difference of action between all containers and that the presence or absence of lipids and trace elements in admixtures stored at 4 degrees C or ambient temperature makes no difference. With exposure to sunlight, vitamin losses were 100% at 3 hours for vitamin A and 50% for vitamin K1; vitamin E concentrations were unchanged after 12 hours of experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Diterpenes↗

Physical compatibility and chemical stability of amphotericin B in combination with magnesium sulfate in 5% dextrose injection.

The physical compatibility and chemical stability of amphotericin B for injection USP (AB) admixed with magnesium sulfate injection USP (MS) in 5% dextrose injection USP (D5W) was evaluated. AB (final concentration of either 40 or 80 micrograms/mL of solution) and MS (final concentration of 0, 2, or 4 mg/mL of solution) were mixed in glass volumetric flasks containing D5W. AB concentration, as quantitated by high-performance liquid chromatography, and visible admixture clarity were monitored at zero, three, and six hours after combining with MS. At the three-hour observation, visible admixture clarity appeared to decrease in all multiple drug combinations and a clear supernatant began to develop as particulates settled to the bottom of the container. MS (final concentration of 4 or 8 mg/mL of solution) and AB (final concentration of 80 micrograms/mL of solution) were prepared in two separate intravenous polyvinyl chloride bags of D5W. The solutions were manually set to infuse via gravity for six hours and mix at the y-site of an intravenous administration set. Samples of the mixture were collected from the terminal end of a primary intravenous administration set at zero, two, four, and six hours after beginning the infusions. Each sample appeared visibly clear and maintained an AB concentration of at least 100 percent of the initial admixture concentration. MS and AB mixed in the same container appeared to be physically incompatible. The same admixture appeared to be physically compatible and chemically stable, in terms of AB, when infused as separate solutions mixed at a y-site of an intravenous administration set.

Amphotericin B↗

Rapid loss of fentanyl citrate admixed with fluorouracil in polyvinyl chloride containers.

OBJECTIVE: To study the physical compatibility and chemical stability of fluorouracil 1 and 16 mg/mL with fentanyl citrate 12.5 micrograms/mL in dextrose 5% and in sodium chloride 0.9% injection. DESIGN: Test solutions of the drugs in dextrose 5% injection and in sodium chloride 0.9% injection were prepared in triplicate and stored at -20, 4, 23, and 32 degrees C. Samples were removed immediately and at various times over 7 days and stored at -70 degrees C until analyzed. Physical compatibility was assessed visually and by measuring turbidity with a color-correcting turbidimeter; particle content was measured with a light-obscuration particle sizer and counter. Chemical stability was determined by measuring the concentration of each drug in the test solutions in duplicate with stability-indicating HPLC. RESULTS: Fentanyl citrate was rapidly lost when admixed with fluorouracil in polyvinyl chloride (PVC) containers, losing about 25% in the first 15 minutes and about 50% in the first hour. The loss of fentanyl citrate was so rapid that accurate time zero determinations were not possible. The extent of fentanyl loss increased with time and occurred more rapidly at the higher temperatures (i.e., 23, 32 degrees C). Losses of 70% or more occurred in all samples within 24 hours. Fentanyl underwent rapid sorption to the containers at the high pH (9.0-9.5) of the fluorouracil admixtures. Adjusting the pH of a fentanyl citrate solution (containing no fluorouracil) in PVC containers to pH 9 with sodium hydroxide also resulted in rapid sorption loss. Fentanyl citrate sorption did not occur when admixtures were prepared in polyethylene containers. Fluorouracil remained stable for at least 7 days at all temperatures. There were no visual or subvisual changes in turbidity or particle content in any of the test solutions at any time. CONCLUSIONS: When admixed with fluorouracil 1 and 16 mg/mL in dextrose 5% injection and sodium chloride 0.9% injection, fentanyl citrate 12.5 micrograms/mL underwent rapid and extensive loss due to sorption to the PVC containers, making the combination unacceptable within minutes of mixing. The sorption results from the alkaline pH of the admixture and, presumably, could occur from the admixture of fentanyl citrate with any sufficiently alkaline drug.

Analgesics, Opioid↗

Stability of fosphenytoin sodium with intravenous solutions in glass bottles, polyvinyl chloride bags, and polypropylene syringes.

OBJECTIVE: To determine the stability of fosphenytoin sodium admixtures with NaCl 0.9% injection and dextrose 5% (D5W) injection when stored in glass or polyvinyl chloride (PVC) containers, to evaluate the compatibility of fosphenytoin with 11 other intravenous solutions, and to determine the stability of fosphenytoin repackaged in polypropylene syringes. METHODS: Dilutions of fosphenytoin sodium 1, 8, and 20 mg phenytoin sodium equivalents (PE)/mL were prepared in NaCl 0.9%, D5W, and 11 other intravenous fluids. Aliquots of each solution in NaCL 0.9% or D5W were transferred to three glass bottles for storage at 25 degrees C and 21 PVC bags for storage at 25, 4, or -20 degrees C. Aliquots of each admixture with the other intravenous fluids were transferred to three PVC bags and stored at 25 degrees C for 7 days. In addition, 63 syringes were filled with fosphenytoin sodium 50 mg PE/mL (undiluted) and stored at 25, 4, or -20 degrees C. Samples of each solution from the three containers were analyzed for visual compatibility, pH, and fosphenytoin concentration initially and at 0.5, 1, 2, 3, 7, 14, and 30 days during storage at 25 and 4 degrees C and at 1, 7, 14, and 30 days during storage at -20 degrees C. Following removal of containers from the freezer, additional samples were obtained after 7 days at 4 or 25 degrees C, and 7 days at 25 degrees C, and then 7 days at -20 degrees C. RESULTS: No visible precipitation or change in color or clarity was observed in any of the fosphenytoin solutions during the study. The concentration of fosphenytoin at each sampling time remained within 97-104% of initial concentration, regardless of container, concentration, intravenous admixture, or storage temperature. CONCLUSIONS: Fosphenytoin sodium, either undiluted in polypropylene syringes or diluted with NaCl 0.9% or D5W in PVC bags, remains stable for at least 30 days at room temperature, under refrigeration, or frozen. After removal from the freezer, fosphenytoin can be thawed, kept at 4 or 25 degrees C for 7 days, and then returned to the freezer for another 7 days. Admixtures of fosphenytoin sodium in various other intravenous fluids are stable for at least 7 days at room temperature.

Chromatography, High Pressure Liquid↗

On modeling locus heterogeneity using mixture distributions.

BACKGROUND: Locus heterogeneity poses a major difficulty in mapping genes that influence complex genetic traits. A widely used approach to deal with this problem involves modeling linkage data in terms of finite mixture distributions. In its simplest setup, also known as the admixture approach, a single parameter is used to model the probability that the disease-causing gene of a family is linked to a reference marker. This parameter is usually interpreted as the overall proportion of linked families. RESULTS: In this article, we address two issues regarding the admixture approach. First, we tackle the question of whether the single parameter of linked proportion is well defined in general. By formulating the likelihood under a classification scheme based on distributions, we show that such a parameter is meaningful only when a certain well-characterized condition is met. Second, we study a condition given in the literature for validating the admixture approach. A counter example is constructed to illustrate that the condition does not necessarily lead to valid estimates. CONCLUSIONS: Estimators from the admixture approach may be inconsistent. This holds even if a condition given in the literature to validate the approach is satisfied.

Chromosome Mapping↗

Physical and chemical compatibility of daptomycin with nine medications.

BACKGROUND: Hospitalized patients with serious gram-positive infections tend to require concomitant therapy. Unfortunately, a number of antimicrobial agents have demonstrated incompatibility with other agents commonly administered intravenously. OBJECTIVE: To evaluate the physical compatibility and chemical stability of the novel lipopeptide antibiotic daptomycin, at 20 mg/mL, with 9 commonly administered intravenous medications: aztreonam, ceftazidime, ceftriaxone, dopamine, gentamicin, fluconazole, heparin, levofloxacin, and lidocaine to support simultaneous Y-site administration. METHODS: Daptomycin was admixed with each medication separately in NaCl 0.9%, incubated at room temperature, and assayed at 30, 60, and 120 minutes. Physical stability was assessed by visual inspection and by turbidity measurements. Chemical stability was assessed by HPLC analysis using standard methods. RESULTS: All 9 daptomycin admixtures remained clear solutions, free of visible particulates. There were also few changes in turbidity (range 0 to -0.7 nephelometric turbidity units) during the study. In general, pH changes were within +/- 0.06 of baseline readings for all admixtures. HPLC analysis indicated no significant reduction (<4%) in daptomycin potency after 120 minutes at room temperature compared with baseline values in all 9 admixtures tested. In addition, there was no significant reduction (<5%) in potency compared with baseline values of the 9 medications tested in the daptomycin admixtures. CONCLUSIONS: The results of this study indicate that solutions of 9 commonly administered intravenous medications simultaneously Y-site administered with daptomycin are stable and compatible, based on both physical and chemical potency analyses.

Anti-Bacterial Agents↗

Three novel mtDNA restriction site polymorphisms allow exploration of population affinities of African Americans.

To develop informative tools for the study of population affinities in African Americans, we sequenced the hypervariable segments I and II (HVS I and HVS II) of mitochondrial DNA (mtDNA) from 96 Sierra Leoneans; European Americans; rural, Gullah-speaking African Americans; urban African Americans living in Charleston, South Carolina; and Jamaicans. We identified single nucleotide polymorphisms (SNPs) exhibiting ethnic affinities, and developed restriction endonuclease tools to screen these SNPs. Here we show that three HVS restriction site polymorphisms (RSPs), EcoRV, FokI, and MfeI, exhibit appreciable differences in frequency (average delta = 0.4165) between putative African American parental populations (i.e., extant Africans living in Sierra Leone and European Americans). Estimates of European American mtDNA admixture, calculated from haplotypes composed of these three novel RSPs, show a cline of increasing admixture from Gullah-speaking African American (m = 0.0300) to urban Charleston African American (m = 0.0689) to West Coast African American (m = 0.1769) populations. This haplotype admixture in the Gullahs is the lowest recorded to date among African Americans, consistent with previous studies using autosomal markers. These RSPs may become valuable new tools in the study of ancestral affinities and admixture dynamics of African Americans.

Africa↗

Was the historic contribution of Spain to the Mexican gene pool partially responsible for the higher prevalence of type 2 diabetes in mexican-origin populations? The Spanish Insulin Resistance Study Group, the San Antonio Heart Study, and the Mexico City Diabetes Study.

OBJECTIVE: Mexican-American populations in San Antonio, Texas (SA-MA) and Mexico have a higher prevalence of type 2 diabetes than non-Hispanic whites in San Antonio (SA-NHW). However, the higher prevalence of type 2 diabetes in Mexican-origin populations might be related, in part, not to Native American genetic admixture but to Spanish genetic admixture. RESEARCH DESIGN AND METHODS: Four population-based epidemiological surveys conducted with Mexican-origin and European-origin samples provided data relevant to this question. In all four surveys, type 2 diabetes was defined as fasting plasma glucose > or =7.0 mmol/l or 2-h glucose > or =11.1 mmol/l or use of antidiabetic agents. RESULTS: A comparison of the two Mexican-origin populations showed that the age- and sex-adjusted prevalence of type 2 diabetes was lower in Mexico than in SA-MA (15.1 vs. 17.9%, P = 0.032). Between the two European-origin populations, the prevalence of type 2 diabetes was lower in SA-NHW than in Spain (6.2 vs. 9.1%, P < 0.0001), but differences were attenuated by adjustment for BMI or after stratification by education. In logistic regression analyses, type 2 diabetes was associated with Mexican ethnic origin after adjusting for age, education, BMI, and waist-to-hip ratio. CONCLUSIONS: The prevalence of type 2 diabetes in Spain was intermediate between that in Mexican-origin populations and SA-NHW. Although the higher degree of Native American admixture is a major contributor to the higher rates of type 2 diabetes, we cannot completely rule out a partial contribution of Spanish admixture to diabetes susceptibility among Mexican- origin populations.

Age Factors↗

Compatibility and stability of linezolid injection admixed with aztreonam or piperacillin sodium.

OBJECTIVE: To evaluate the physical compatibility and chemical stability of linezolid (Zyvox-Pharmacia) 200 mg/100 mL admixed with aztreonam (Azactam-Squibb) 2 grams and separately with piperacillin sodium (Pipracil-Lederle) 3 grams over 7 days at 4 degrees C and 23 degrees C. DESIGN: Controlled experimental trial. SETTING: Laboratory. INTERVENTIONS: Test samples were prepared by adding the required amount of aztreonam or piperacillin sodium to separate bags of linezolid injection 200 mg/100 mL. MAIN OUTCOME MEASURES: Physical compatibility and chemical stability based on drug concentrations initially and after 1, 3, 5, and 7 days of storage at 4 degrees C and 23 degrees C. RESULTS: All of the linezolid admixtures with aztreonam and with piperacillin sodium were clear when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low and exhibited little change throughout the study at both storage temperatures. High-performance liquid chromatography analysis found little or no loss of linezolid in any sample stored at either temperature throughout the study. Aztreonam in the linezolid admixtures was stable for 7 days, exhibiting less than 5% loss at 4 degrees C and 9% loss at 23 degrees C. Piperacillin sodium in the linezolid admixtures was stable for 7 days at 4 degrees C, exhibiting no loss, but was stable for only 3 days at 23 degrees C with losses of about 5%. Losses had increased to 9% to 12% after 5 days of storage at room temperature. CONCLUSION: Admixtures of linezolid 200 mg/100 mL with aztreonam 2 grams or piperacillin sodium 3 grams were physically compatible and chemically stable for at least 7 days stored at 4 degrees C and for 7 days or 3 days, respectively, at 23 degrees C.

Acetamides↗

[Genetic composition of Chilean population: rural communities of Elqui, Limari and Choapa valleys].

BACKGROUND: The population that inhabits the semiarid Northern zone of Chile arose from ethnic admixture between aborigines, Spanish conquerors and the influx, during the XVII century, of foreign aboriginal workers and a minority of African slaves. AIM: To study the phenotypic frequencies of 15 genetic markers among populations inhabiting valleys in the Northern zone of Chile and to estimate the percentage of indigenous, African and Caucasian admixture in these populations. MATERIAL AND METHODS: Throughout five different field works, blood samples were obtained from 120 individuals living in the Elqui valley, 120 individuals living in the Limari valley and 85 living in the Choapa valley. Blood groups, erythrocyte enzymes, plasma proteins and HLA markers were typified. RESULTS: In the populations studied, the contribution of non indigenous genes was low in relation with the time elapsed since the Spanish invasion. The Hardy-Weinberg disequilibrium for MNS system would have microevolutive implications. The admixture percentages in these valleys confirm ethnic and historic information. The variation of the enzyme esterase D is identical to that of other Chilean populations. CONCLUSIONS: The phenotypic and genetic frequencies in the three populations studied and different admixture of indigenous genes is inversely proportional to the geographic distance from Santiago, in Central Chile.

Blood Group Antigens↗

Stability and sorption of FK 506 in 5% dextrose injection and 0.9% sodium chloride injection in glass, polyvinyl chloride, and polyolefin containers.

The effects of the diluent, the storage container, light, and infusion through various types of tubing on the stability and sorption of FK 506 were studied. Solutions of FK 506 in 0.9% sodium chloride injection or 5% dextrose injection were stored at room temperature (24 +/- 2 degrees C) in glass i.v. bottles, polyvinyl chloride (PVC) minibags, and polyolefin containers. FK 506 solution in 0.9% sodium chloride injection was stored in plastic syringes at room temperature and either exposed to normal room light or stored in the dark. FK 506 solution in 5% dextrose injection was placed in plastic syringes and infused through PVC anesthesia extension tubing, PVC i.v. administration set tubing, and fat emulsion tubing over a two-hour period. The infused samples and samples collected from the containers and syringes at intervals up to 48 hours were analyzed for FK 506 concentration by high-performance liquid chromatography. FK 506 concentrations remained greater than 90% of initial concentration for admixtures in 5% dextrose injection stored in glass bottles for 48 hours and for admixtures in 5% dextrose injection or 0.9% sodium chloride injection stored in polyolefin containers for 48 hours. No change in concentration was measured for admixtures in 0.9% sodium chloride injection stored in plastic syringes, and exposure to light did not affect the stability of FK 506 solution. No substantial change in concentration occurred in FK 506 solution in 5% dextrose injection infused through PVC anesthesia extension tubing, PVC i.v. administration set tubing, or fat emulsion tubing. FK 506 admixtures prepared with 5% dextrose injection or 0.9% sodium chloride injection should be stored in polyolefin containers. If polyolefin containers are not available, solutions should be prepared with 5% dextrose injection and stored in glass bottles.

Adsorption↗

Practical guidelines for preparing and administering amphotericin B.

Current practices used in the preparation and administration of amphotericin B are evaluated, and updated guidelines are presented. Intravenous admixtures of amphotericin B 0.25 and 1.4 mg/mL in 5% dextrose injection have an expiration date of 35 days and 36 hours, respectively. Since commercial formulations of amphotericin B lack a bacteriostatic agent, admixtures should be stored at 4-8 degrees C. Protection from fluorescent light is unnecessary. Admixtures may be prepared in polyolefin, glass, or polyvinyl chloride intravenous containers; certain evacuated intravenous containers contain buffers that can cause precipitation of amphotericin B. The addition of a buffering agent to the intravenous admixture is unnecessary when the initial pH of the 5% dextrose injection exceeds 4.2. The usual daily maintenance dose of amphotericin B is 0.5-1 mg/kg i.v. The manufacturer recommends beginning intravenous therapy with a 1-mg test dose. The initiation of therapy with incrementally increased doses may be detrimental if it delays the delivery of a therapeutic dose. Amphotericin B can be infused over one to two hours (less than or equal to 50 mg/hr) in patients with adequate renal function. Bladder instillation of amphotericin B 50 mg in 1 L of sterile water has been used to treat fungal cystitis. Ancillary medications administered to treat infusion-related adverse events should be used as prophylaxis in patients with a history of hypersensitivity or unacceptable reactions and as needed for relief of symptoms. Sodium supplementation should be implemented cautiously, on a patient-specific basis.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphotericin B↗

Stability of fluorouracil, cytarabine, or doxorubicin hydrochloride in ethylene vinylacetate portable infusion-pump reservoirs.

The stability of fluorouracil, cytarabine, and doxorubicin hydrochloride in admixtures stored in portable infusion-pump reservoirs was investigated. Admixtures containing fluorouracil 50 or 10 mg/mL, cytarabine 25 or 1.25 mg/mL, or doxorubicin hydrochloride 1.25 or 0.5 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection were placed in 80-mL ethylene vinylacetate drug reservoirs protected from light, and 1-mL quantities were withdrawn immediately after preparation and after storage for 1, 2, 3, 4, 7, 14, and 28 days at 4, 22, or 35 degrees C. For each condition, three samples from each admixture were tested for drug concentration by stability-indicating high-performance liquid chromatography. The admixtures were also monitored for precipitation, color change, and pH. Evaporative water loss from the containers was measured. Fluorouracil was stable at all temperatures for 28 days. Cytarabine was stable for 28 days at 4 and 22 degrees C and for 7 days at 35 degrees C. Doxorubicin hydrochloride was stable for 14 days at 4 and 22 degrees C and for 7 days at 35 degrees C. No color change or precipitation was observed, and pH values were stable. Loss of water through the reservoirs was substantial only at 35 degrees C for 28 days. When stored in ethylene vinylacetate portable infusion-pump reservoirs, fluorouracil, cytarabine, and doxorubicin hydrochloride were each stable for at least one week at temperatures up to 35 degrees C. Cytarabine and doxorubicin hydrochloride showed decreasing stability at longer storage times and higher temperatures.

Cytarabine↗