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Gm 3;5,13,14 and stated-admixture: independent estimates of admixture in American Indians.

Bernstein's formula for the estimation of the amount of admixture (m) in a hybrid population has been used frequently since its publication in 1931. While mathematically correct, it has not been shown to be correct in practice, because an independent estimate from a large sample has not been available. We have compared the estimate of m for Caucasian admixture derived by using Bernstein's formula with that estimated from stated-admixture (Sa) within a sample of 5,759 Native Americans. There was a linear relationship between the two variables (m = -.000275 + .714Sa; r = .976 for the grouped data, P = .0001).

Gene Frequency

Stability of mitomycin admixtures.

The stability of mitomycin in admixtures for continuous intravenous infusion was studied. Mitomycin was reconstituted and diluted to 50 micrograms/mL in polyvinyl chloride minibags containing 5% dextrose injection 50 mL or 0.9% sodium chloride injection 50 mL. Additional mitomycin admixtures were reconstituted with a buffer solution containing monobasic and dibasic sodium phosphate; these were diluted with 5% dextrose injection only. Admixtures were stored at room temperature (27-30 degrees C) and refrigerated temperature (5 degrees C) for 120 days. Mitomycin concentrations in each admixture were tested by high-performance liquid chromatography (HPLC) immediately after admixture and at intervals during storage. Ultraviolet spectra were determined at the same time as HPLC analysis, and the admixtures were visually inspected and tested for pH. Mitomycin concentrations decreased rapidly in the unbuffered admixtures; after 12 hours at room temperature, less than 26% of the drug remained in the dextrose admixture. When the unbuffered admixtures were refrigerated for 12 hours, the mitomycin concentrations decreased 10% in the sodium chloride admixtures and 33% in the dextrose admixtures; after 24 hours, the percentages of drug loss were 23% and 42%, respectively. Mitomycin concentrations in the buffered admixtures showed no substantial decrease during 120 days at 5 degrees C. At room temperature, concentrations decreased 10% after 15 days. When the admixture is buffered to a pH of approximately 7.8, mitomycin is stable in 5% dextrose injection for up to 15 days at room temperature and at least 120 days at 5 degrees C. Unbuffered mitomycin admixtures should not be stored or administered by prolonged i.v. infusion.

Chromatography, High Pressure Liquid

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

Stability of intravenous admixtures of aztreonam and cefoxitin, gentamicin, metronidazole, or tobramycin.

The stability of aztreonam and cefoxitin, gentamicin, metronidazole, or tobramycin in intravenous admixtures containing aztreonam and one of the other drugs was studied. Admixtures of aztreonam and gentamicin, aztreonam and tobramycin, and aztreonam and cefoxitin were each prepared in four different concentrations in both 0.9% sodium chloride injection and 5% dextrose injection. Admixtures of aztreonam and metronidazole were prepared in two different concentrations using a commercially available solution of metronidazole 5 mg/mL in a phosphate-citrate buffer. One of each of these admixtures was stored at 25 degrees C for 48 hours and at 4 degrees C for seven days. At various storage times, 1-mL samples of the admixtures were tested for pH and assayed using high-performance liquid chromatography or fluorescence polarization immunoassay. The pH of all admixtures except admixtures of aztreonam and cefoxitin decreased only slightly during storage. Concentrations of aztreonam and tobramycin under both storage conditions decreased by less than 10%. Concentrations of cefoxitin and aztreonam decreased by more than 10% at 25 degrees C, and concentrations of gentamicin decreased by more than 10% under both storage conditions. Visual inspection of admixtures of aztreonam and metronidazole revealed an incompatibility between the two drugs, as evidenced by the appearance of a cherry-red color. Admixtures of aztreonam 10 and 20 mg/mL and tobramycin 0.2 and 0.8 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection are stable for 48 hours at 25 degrees C or seven days at 4 degrees C. Admixtures of aztreonam 10 and 20 mg/mL and gentamicin 0.2 and 0.8 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection are stable for eight hours at 25 degrees C and 24 hours at 4 degrees C. Admixtures of aztreonam 10 and 20 mg/mL and cefoxitin 10 and 20 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection are stable for 12 hours at 25 degrees C and seven days at 4 degrees C. Aztreonam and metronidazole should be administered separately.

Aztreonam

Fat emulsion particle-size distribution in total nutrient admixtures.

The fat particle-size distribution in and physical stability of two commercially available lipid emulsions before and after their use in total nutrient admixtures (TNAs) are reported. Four TNAs without electrolytes and four TNAs with electrolytes were prepared; each type of TNA was prepared with Liposyn II and with Intralipid. Particle size was measured in the < 1-micron range by using photon correlation spectroscopy and in the 2-60-microns range by using light blockage. Admixtures with or without electrolytes were stored for two or nine days at 4 degrees C followed by one day at 25 degrees C. For the fraction of fat particles of < 1 micron in diameter, Intralipid and Liposyn II had a mean particle size of 374 and 313 nm, respectively. The admixtures containing electrolytes showed a decrease in mean particle size of about 7%. Admixtures with Intralipid contained 2 x 10(7) particles larger than 2 microns per milliliter (1.7% of total fat), compared with 1 x 10(6) particles per milliliter (0.05-0.15% of total fat) for admixtures with Liposyn II. The addition of electrolytes increased the particle counts for Liposyn II-containing admixtures. Upon storage, Intralipid-containing admixtures with electrolytes showed an initial increase followed by a decrease in the mean diameter of particles of < 1 micron. All the admixtures were stable in terms of pH and visual appearance. Intralipid-containing admixtures with electrolytes showed a decrease in the number of particles in the 2-60-microns size range, while Liposyn II-containing admixtures with electrolytes showed an increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Incompatibility

Stability of cisplatin and etoposide in intravenous admixtures.

The stability of various concentrations of etoposide and cisplatin in intravenous admixtures under various storage conditions was studied. Admixtures containing etoposide (200 and 400 micrograms/mL) with cisplatin (200 micrograms/mL) were prepared in 0.9% sodium chloride injection and in 5% dextrose and 0.45% sodium chloride injection. The admixtures were stored in either polyvinyl chloride bags or glass bottles. Mannitol and potassium chloride were added to selected admixtures. Half of the admixtures were protected from light, while the other half were exposed to fluorescent light. All admixtures were stored at room temperature. Samples were visually inspected and assayed for etoposide and cisplatin content by high-performance liquid chromatography within 15 minutes after admixture preparation and after 8, 24, and 48 hours of storage. Etoposide and cisplatin concentrations decreased less than 10% from the initial concentration after eight hours of storage. At 24 hours, the admixtures containing etoposide 400 micrograms/mL and cisplatin 200 micrograms/mL (with additives) in 0.9% sodium chloride injection precipitated. The decrease in etoposide concentrations during the first 24 hours in the rest of the admixtures was less than 10% of the initial concentration. The change in etoposide concentration was related to the type of i.v. solution and the presence of additives. After 24 hours, the change in cisplatin concentrations was less than 10% of the initial concentration, except in the admixtures that precipitated. For cisplatin, the presence of light was related to an increased loss of cisplatin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid

Effects of pH, temperature, concentration, and time on particle counts in lipid-containing total parenteral nutrition admixtures.

It has been standard practice in the United States to separate lipid emulsion from the other components of total parenteral nutrition (TPN) due to the reported instability of admixed intravenous lipid emulsions. Some clinicians, however, have combined all TPN components into one container and administered these admixtures to patients without apparent difficulties. Infusion of all nutrients from one container has many advantages. In this study standard and concentrated admixtures were aseptically prepared using generally accepted guidelines of the nutritional requirements for a 70-kg patient. Treatments of standard and concentrated admixtures consisted of: storing at 4 degrees C without adjusting the pH; increasing the pH to 6.6 and storing at 4 degrees C; increasing the pH to 6.6 and storing at room temperature. Samples were monitored for 3 weeks by means of Coulter Counter analysis, pH determinations, and visual observations. The pH of the admixtures did not change over 3 weeks. Mean counts of particles with sizes between 1.6 and 25.4 mu increased over time for each treatment group. Within treatments, concentrated admixtures had significantly greater particle counts than the corresponding standard admixtures. Within the standard and within the concentrated admixtures, the particle counts were significantly greater for group one than for group three. Particle counts in group two tended to lie between the values of group one and three. Visual signs of emulsion deterioration were greatest in those admixtures in which the pH was not adjusted and occurred earlier in concentrated admixtures.

Amino Acids

Stability of ranitidine in intravenous admixtures stored frozen, refrigerated, and at room temperature.

The stability of ranitidine in concentrations of 0.5, 1.0, and 2.0 mg/mL in admixtures with commonly used i.v. fluids was studied. The admixture vehicles were 0.9% sodium chloride, 5% dextrose, 10% dextrose, 5% dextrose and 0.45% sodium chloride, and 5% dextrose with lactated Ringer's (DLR) injections in polyvinyl chloride bags. Three bags were prepared for each test solution and stored under each of the following conditions: seven days at room temperature (23 +/- 1 degrees C) in normal laboratory lighting, 30 days at 4 degrees C, and 60 days at -20 degrees C followed by either seven days at room temperature (in light) or 14 days at 4 degrees C. Ranitidine content was determined by high-performance liquid chromatography at several intervals. Color, clarity, and pH were also examined. Ranitidine concentrations remained greater than or equal to 90% of initial concentrations under all storage conditions except in the frozen DLR admixtures. Drug loss in the DLR admixtures was greatest at the lower ranitidine concentrations. The only visual changes were yellow color in the thawed DLR admixtures and those containing ranitidine 2.0 mg/mL in 5% dextrose and 0.45% sodium chloride. Slight increases in the pH of some admixtures were noted. Ranitidine is stable for seven days at room temperature and 30 days at 4 degrees C at all concentrations and in all vehicles studied. At the studied concentrations, the drug is stable in admixtures frozen for 60 days and stored for seven days at room temperature or 14 days refrigerated, except in DLR admixtures; these admixtures should not be stored frozen.

Drug Combinations

Personnel time and preparation costs for compounded versus premixed intravenous admixtures in three community hospitals.

Personnel time requirements and costs associated with the ordering, preparation, and administration of manually compounded versus premixed i.v. admixtures were determined at three for-profit community hospitals. The three hospitals, all owned by one corporation, ranged in size from 160 to 239 beds. At each hospital, pharmacists or technicians manually compounded admixtures in glass bottles or plastic bags. Work flow descriptions of the activities involved in the preparation and administration of admixtures were created, and time-motion and work-sampling techniques were used to observe three to five pharmacists or technicians in each hospital over a seven-day period. Drug waste also was monitored. At the conclusion of the baseline study, each hospital switched to the premixed products that they had chosen to evaluate; admixtures of cefazolin sodium, cefoxitin sodium, gentamicin sulfate, and potassium chloride were available. After a two-week acclimation period, the seven-day study was repeated. Average total labor time ranged from 5.6 to 9.1 minutes per compounded admixture to 4.1 to 7.7 minutes per premixed admixture. The percentage of total labor time devoted to compounding, delivering, stocking, and other physical handling of materials decreased by 64% for admixtures of gentamicin or potassium chloride and by 67% for admixtures of cefazolin or cefoxitin. The average reduction in annual costs for accessories, labor time, wasted drugs, and inventory at each hospital was +15,000. Additional savings were realized from overall lower acquisition costs for the premixed products at the study hospitals. The use of premixed i.v. admixtures reduced preparation time and labor and material costs in three small- and medium-sized community hospitals.

Costs and Cost Analysis

Stability of cimetidine hydrochloride in a total nutrient admixture.

The stability of cimetidine hydrochloride in a total nutrient admixture was studied. A total nutrient admixture composed of 5% amino acid injection, 20% dextrose injection, and 3% intravenous fat emulsion was prepared aseptically in four 2-L ethylene-vinyl acetate bags. Cimetidine hydrochloride injection was added to three of the admixtures to yield final cimetidine concentrations of 600, 1200, and 1800 mg per 1500 mL of admixture; the fourth admixture served as a control. At 0, 24, and 48 hours, cimetidine content was measured by high-performance liquid chromatography, and the admixtures were tested for pH and visually inspected for signs of creaming, oiling out, or phase separation. Particle-size distribution in the admixtures was compared with that in 20% intravenous fat emulsion. No appreciable changes in cimetidine concentration or pH occurred over 48 hours, and no visual changes were observed. Particle sizes were comparable to those in the 20% intravenous fat emulsion control except in the admixture containing cimetidine hydrochloride 600 mg, which had significantly more particles larger than 9.9 microns at 48 hours. In the total nutrient admixture studied, cimetidine hydrochloride in concentrations up to 1800 mg per 1500 mL was stable for 24 hours at room temperature, and the lipid emulsion was apparently not altered during this period by cimetidine.

Chromatography, High Pressure Liquid

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

Recombination of haplotypes leads to biased estimates of admixture proportions in human populations.

A population formed by genetic admixture of two or more source populations may exhibit considerable linkage disequilibrium between genetic loci. In the presence of recombination, this linkage disequilibrium declines with time, a fact that is often ignored when considering haplotypes of closely linked systems [e.g., Gm serum group (gamma globulins), HLA, and, more recently, restriction fragment length polymorphisms]. Recombination alters haplotype frequencies over time, and the haplotype-derived measures of admixture proportions from haplotype frequencies in generations following the admixture event become progressively more biased. The direction and extent of this bias can be predicted only when the history of admixture is known. Numerical illustration suggests that this bias is problematic whenever rt greater than 0.05, where r is the recombination rate between linked loci and t is the time (in generations) that has elapsed since the admixture event. In general, even the haplotype frequencies defined by multiple restriction fragment length polymorphism should be used with caution for admixture analysis. When recombination rates or the time since admixture are not precisely known, it is advantageous to consider each restriction fragment length polymorphism site separately for admixture analysis.

Algorithms

Admixture studies and the detection of selection.

Three methods can be used to search for evidence of natural selection from admixture studies. These include classification of the admixture estimates into two groups; calculation of the rank correlation between estimates from more than one population; and the testing of admixture estimates for homogeneity. The use of these methods is discussed with special reference to black-white admixture in the United States. Using revised estimates of African gene frequencies, derived from a consideration of the geographical origin of the slaves, we calculated admixture estimates and their variances for five U.S. black populations; Claxton (Georgia); Sapelo Island (Georgia); James Island (South Carolina); Charleston (South Carolina); Oakland (California). Two out of the five populations yielded heterogeneous admixture estimates but all other tests were non-significant. The data provide little evidence for the action of selection. The few, inconsistent significant results are more indicative of the action of random drift or biased gene frequency estimates than natural selection, and in general these effects cannot be differentiated. It seems doubtful that admixture studies can ever provide unequivocal evidence for the action of natural selection in human populations. In the search for natural selection, perhaps admixture studies should only be used as a preliminary screening device.

Black People

Stability of amrinone and digoxin, procainamide hydrochloride, propranolol hydrochloride, sodium bicarbonate, potassium chloride, or verapamil hydrochloride in intravenous admixtures.

The stability of amrinone and digoxin, procainamide hydrochloride, propranolol hydrochloride, sodium bicarbonate, potassium chloride, or verapamil hydrochloride in intravenous admixtures was studied. Admixtures of amrinone and digoxin were studied at one concentration. Amrinone admixtures with propranolol hydrochloride, sodium bicarbonate, potassium chloride, and verapamil hydrochloride were studied at two concentrations. In general, 0.45% sodium chloride injection was used as the diluent; 5% dextrose injection was also used for the procainamide hydrochloride experiments. Duplicate solutions of each test admixture and single-drug control admixture were prepared and stored for four hours at 22-23 degrees C under fluorescent light. Samples were analyzed by visual inspection, tested for pH, and assayed by high-performance liquid chromatography. Admixtures containing amrinone 1.25 or 2.5 mg/mL (as the lactate salt) and sodium bicarbonate 37.5 mg/mL precipitated immediately or within 10 minutes. No changes in pH or visual appearance were noted for amrinone admixtures with procainamide hydrochloride, digoxin, propranolol hydrochloride, potassium chloride, and verapamil hydrochloride. Appreciable degradation of both amrinone and procainamide was observed after four hours when the two were mixed in 5% dextrose. No degradation of amrinone or procainamide was seen when the 5% dextrose was replaced by 0.45% sodium chloride. Amrinone and sodium bicarbonate were incompatible in intravenous admixtures. Amrinone was compatible with digoxin, propranolol hydrochloride, potassium chloride, and verapamil hydrochloride. Amrinone and procainamide were compatible in 0.45% sodium chloride injection but not in 5% dextrose injection.

Amrinone

Stability of various total nutrient admixture formulations using Liposyn II and Aminosyn II.

The compatibility of a safflower oil-soybean oil lipid emulsion (Liposyn II) with dextrose and amino acid injection (Aminosyn II) with or without electrolytes was studied in total nutrient admixtures (TNAs). The admixtures studied were divided into two groups. In group 1, 15 admixtures representing six different combinations of Liposyn II, Aminosyn II, and dextrose injection were studied. In group 2, nine admixtures representing nine combinations of Liposyn II, Aminosyn II with Electrolytes, and dextrose injection were studied. Both 10% and 20% concentrations of the fat emulsion, amino acid concentrations of 7, 8.5, and 10%, and dextrose injections of 10, 40, 50, and 70% were used. The core admixture components were placed in an ethylene vinyl acetate container in the following sequence: fat, amino acids, dextrose. One of two combinations of electrolytes and trace metals was added to each admixture at the end of mixing. Multivitamins were added to each TNA just before 24-hour storage at room temperature (25 +/- 4 degrees C). Four admixtures were tested after one day at room temperature, six after two days at 5 degrees C plus one day at 30 degrees C, and 14 after nine days at 5 degrees C plus one day at room temperature. Measurements of pH, emulsion particle size, and zeta potential (electrostatic surface charge of lipid particles) were made after visual inspection of each admixture. Concentration of individual amino acids and dextrose were determined by appropriate chromatographic techniques initially and at the end of the storage period. The TNAs retained a uniform, milk-like appearance under all storage conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids

Effect of phototherapy light, sodium bisulfite, and pH on vitamin stability in total parenteral nutrition admixtures.

The three sections of this study extend previous research into losses of vitamins A, C, E, thiamin, riboflavin, and folic acid from total parenteral nutrition (TPN) admixtures. First, phototherapy light on TPN admixtures containing one of four amino acid solutions was studied. Experimental conditions included presence or absence of Intralipid iv fat emulsion, plastic bag or glass bottle storage container, and storage time of up to 48 hrs. The second phase studied stability of the same vitamins (except vitamin E) for 48 hrs in admixtures containing the amino acid solution which has no bisulfite, in glass bottles; with or without Intralipid; and with added sodium bisulfite (final concentrations of 0, 1, 2, 3, 4, 5 and 10 mEq/liter). Third, vitamin C and thiamin levels were measured in admixtures containing the amino acid solution with no bisulfite, without Intralipid, stored in glass bottles with various bisulfite concentrations (0, 1, 2, or 3 mEq/liter) and three pH levels (5.5, 6.5, and 6.75 pH). Exposure of TPN admixtures to phototherapy light caused losses of vitamins A, C, and riboflavin. Intralipid inclusion significantly reduced losses of vitamin A and riboflavin, but did not appear to affect vitamin C levels. The smallest vitamin C losses were noted in admixtures containing amino acid solutions A or B. Phototherapy light did not affect thiamin levels. Bisulfite had no affect on vitamin C, riboflavin, or folic acid levels. Vitamin A levels were maintained with bisulfite concentrations less than 3 mEq/liter. At 3 mEq/liter bisulfite, admixtures with Intralipid showed 50% loss of vitamin A.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Stability

Emulsion stability in total nutrient admixtures containing a pediatric amino acid formulation.

Emulsion stability of total nutrient admixtures containing TrophAmine amino acid injection admixed with Intralipid, Nutrilipid, and Liposyn II was studied. High and low electrolyte concentrations were added to each total nutrient admixture before storage at 4 degrees C for 48 hours then at 20-22 degrees C for 24 hours. Stability studies were also performed on total nutrient admixtures containing higher concentrations of fat emulsion and total nutrient admixtures with added cysteine hydrochloride and carnitine. High electrolyte concentrations only were added to these total nutrient admixtures before being stored refrigerated for 24 hours then at room temperature for 24 hours. Visual assessment, pH determination, and particle size analysis were performed immediately after compounding and after refrigerated and room temperature storage. Particle size was assessed by measuring the mean diameter of the fat emulsion and the percent of oil volume in particles greater than 5 microns. Repeated-measures analyses of variance were used to determine significance of type or concentration of fat emulsion, electrolyte concentrations, or time on mean diameter or percent particles greater than 5 microns. There were minimal changes in pH values over time. Creaming was observed in all total nutrient admixtures at all sampling times except time zero. This was reversible upon agitation. Results of particle size analysis over time indicated little change in mean diameter or percent particles greater than 5 microns. These minimal changes did not seem to be clinically significant. It is concluded that total nutrient admixtures prepared with this pediatric amino acid formulation are stable when prepared and stored as reported.

Amino Acids

Intropin (dopamine hydrochloride) intravenous admixture compatibility. Part 2: stability with some commonly used antibiotics in 5% dextrose injection.

The stability of dopamine hydrochloride (Intropin) and several commonly used antibiotics was studied as admixtures in 5% Dextrose Injection USP. The antibiotic-dopamine-dextrose 5% admixtures were assayed for dopamine by colorimetric and chromatographic procedures. The antibiotics were assayed by standard microbiological methods. Kanamycin sulfate, tetracycline hydrochloride, carbenicillin disodium and chloramphenicol sodium succinate were stable in the Intropin-5% dextrose admixture for a period of 24 hours at room temperature in fluorescent and natural (western exposure) light. Gentamicin sulfate, penicillin G potassium and cephalothin sodium were stable in Intropin-5% dextrose admixture for six hours. Ampicillin sodium was stable in the Intropin admixture for only one hour. Amphotericin B was physically unstable in the Intropin-dextrose 5% solution upon admixture. The potency of dopamine hydrochloride remained substantially unchanged in the presence of the above antibiotics. It is recommended that dopamine not be added to amphotericin B or ampicillin sodium admixtures. Further, in order to avoid a fixed combination of potent drugs, it is recommended that a "piggyback" administration set or administration into a second injection site be employed when another drug is to be administered with dopamine hydrochloride.

Anti-Bacterial Agents