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PubMed1989

Compatibility of aminophylline and verapamil in intravenous admixtures.

The chemical and visual compatibility of aminophylline and verapamil hydrochloride in intravenous admixtures was evaluated. Verapamil hydrochloride injection was added to a solution of aminophylline 1.0 mg/mL in 5% dextrose injection (D5W) to yield final verapamil hydrochloride concentrations of 0.1 and 0.4 mg/mL. Each solution type was prepared in triplicate. An aliquot from each of these solutions was assayed in duplicate for theophylline and verapamil by high-performance liquid chromatography at 0, 4, 8, 12, and 24 hours after mixing. All aliquots were filtered with a 0.22-micron filter immediately before assay. At each time interval, samples were assessed for pH and inspected visually and microscopically for evidence of incompatibility. Theophylline concentrations showed less than 10% change over 24 hours in the two-drug admixtures. Less than 1% of the original verapamil concentrations remained immediately after mixing with aminophylline injection in D5W. Turbidity was readily apparent in the admixture containing verapamil hydrochloride 0.4 mg/mL; however, microscopic evaluation revealed precipitate in both solutions. Solution pH was determined to be a primary cause of precipitation. The mean pH values for the verapamil hydrochloride 0.1 and 0.4 mg/mL control solutions were 4.09 and 4.36, respectively. The mean pH of the aminophylline 1.0 mg/mL control solution was 8.35. The mean pH of the aminophylline-verapamil admixtures at verapamil hydrochloride concentrations of 0.1 and 0.4 mg/mL was 8.14 and 8.06, respectively. Verapamil hydrochloride injection in final concentrations of 0.1 and 0.4 mg/mL is incompatible with aminophylline 1.0 mg/mL in D5W.

Aminophylline↗
PubMed1986

Practical considerations regarding the use of total nutrient admixtures.

The biological concerns, proper storage and administration, and advantages of using total nutrient admixtures (TNAs) for nutritional support are reviewed. In 1983, FDA approved lipid emulsions for administration with dextrose and selected crystalline amino acid preparations (known as three-in-one or total nutrient admixtures). The stability of TNAs is affected by pH, order of mixing, and temperature. Conflicting results have been reported on the issue of microbial growth potential in TNAs. At room temperature, the delivery of the TNA infusate should not exceed 24 hours. Plastic containers that do not contain diethylhexyl phthalate, in sizes up to 3 L, are practical and safe for administration of TNAs. The efficiency of an institution's volumetric pumps should be evaluated before converting to a TNA system because the low final concentrations of lipid emulsion present in the admixtures may render certain pumps inoperable. The practical, nutritional, and potential economic benefits of a TNA delivery system support its use. Further research is needed to determine microbial growth potential, electrolyte and drug compatibilities, and stability under prolonged storage of these admixtures.

Drug Compounding↗
PubMed1986

Personnel costs and preparation time in a centralized intravenous admixture program.

The amount of time and the cost of personnel time associated with the preparation of injectable products were determined. A time study consisting of 9041 observations during a seven-day period was conducted to determine the amount of time required of pharmacists and technicians for the preparation of total parenteral nutrient (TPN) solutions, large-volume injectables, antibiotic admixtures, antineoplastic admixtures, and investigational drugs. The established times were used to calculate relative value units for each product line and to determine the cost of pharmacist and technician time associated with the preparation of each product line. Preparation times ranged from 3.7 minutes for an antibiotic admixture to 49 minutes for a pediatric TPN solution. Total personnel costs ranged from $0.71 for an antibiotic admixture to $10.70 for a pediatric TPN solution. The calculated relative value units indicated that existing departmental time standards did not allow sufficient time for the preparation of some products. Establishing relative value units and calculating the cost of personnel time associated with the preparation of injectable products can be helpful for comparing the cost of purchasing ready-to-use products with the cost of preparing the same products.

Costs and Cost Analysis↗
PubMed1988

Stability of ranitidine hydrochloride in total nutrient admixtures.

The stability of ranitidine hydrochloride in total nutrient admixtures (TNAs) containing 5% intravenous fat emulsion was studied. A TNA containing lipids and glucose was prepared aseptically in three ethylene-vinyl acetate bags. Ranitidine hydrochloride 100 mg and 200 mg was added to two of the bags to yield concentrations of 50 micrograms/mL and 100 micrograms/mL, respectively. The third bag served as a control. At 0, 12, 24, 48, and 72 hours, the ranitidine content was measured by high-performance liquid chromatography, the pH of the admixtures was determined, and the bags were visually inspected for signs of color changes, creaming, or precipitates. Particle-size distribution was measured at 72 hours and compared with that in the control bag at time zero. No appreciable changes in pH occurred over 72 hours, and no visual changes were observed. At concentrations of 50 and 100 micrograms/mL of admixture, ranitidine hydrochloride activity declined approximately 80% during the study period. Approximately 10% of the initial concentration was lost in 12 hours. In both cases, there was no variation in particle-size distribution compared with that in the control bag at time zero. Ranitidine hydrochloride appears to be stable for up to 12 hours at room temperature in the admixtures studied, and the lipid emulsion apparently was not altered during this period by ranitidine.

Chemical Phenomena↗
PubMed1987

Compatibility of premixed theophylline and methylprednisolone sodium succinate intravenous admixtures.

The stability of theophylline supplied as a premixed injection and of methylprednisolone sodium succinate in admixtures containing both drugs was studied. Solutions containing theophylline in concentrations of 4.0 mg/mL and 0.4 mg/mL were used. Methylprednisolone sodium succinate was added to each solution to produce a final concentration of 0.5 mg/mL and 2.0 mg/mL of methylprednisolone alcohol, a pharmacologically active form of methylprednisolone sodium succinate. Each admixture was prepared in triplicate, and samples were kept at room temperature in glass containers. Immediately after admixture and at 3, 6, 12, and 24 hours, samples were visually inspected, tested for pH, filtered, and assayed in duplicate by high-performance liquid chromatography for theophylline concentration and for both methylprednisolone sodium succinate and methylprednisolone alcohol content. Control solutions containing only one of the two drugs were also tested. No visual changes were observed. The addition of theophylline in 5% dextrose injection to the methylprednisolone sodium succinate solutions resulted in decreased pH values for all solutions, which did not vary significantly throughout the study period. Theophylline concentrations did not change significantly compared with baseline. In solutions containing theophylline 0.4 mg/mL with either 2.0 or 0.5 mg/mL of methylprednisolone sodium succinate, less than 90% of the initial methylprednisolone sodium succinate concentrations remained at 24 hours. However, within three hours after admixture preparation, methylprednisolone alcohol was detected in those solutions in increasing concentrations. A commercial preparation of premixed theophylline in 5% dextrose injection in a concentration of 4 mg/mL or less can be mixed with methylprednisolone sodium succinate in a final concentration of 2 mg/mL or less and administered intravenously within 24 hours after mixing.

Chromatography, High Pressure Liquid↗
PubMed1986

Stability of intravenous admixtures containing aztreonam and cefazolin.

The stability of aztreonam and cefazolin in intravenous admixtures was studied. Each of the following combinations of drugs was added to both 5% dextrose injection and 0.9% sodium chloride injection in polyvinyl chloride containers: aztreonam 20 mg/mL and cefazolin 20 mg/mL (as the sodium salt); aztreonam 10 mg/mL and cefazolin 5 mg/mL; aztreonam 20 mg/mL and cefazolin 5 mg/mL; and aztreonam 10 mg/mL and cefazolin 20 mg/mL. One of each of these admixtures was stored at 23-25 degrees C for 48 hours and at 4-5 degrees C for seven days. At various storage times the admixtures were inspected for visual changes, and 1-mL samples were tested for pH and assayed using a stability-indicating high-performance liquid chromatographic assay. No visual changes were observed, and changes in pH were negligible. Concentrations of aztreonam and cefazolin under both storage conditions decreased by less than 3%. Intravenous admixtures of aztreonam and cefazolin at the concentrations studied are stable for at least 48 hours at 23-25 degrees C and for seven days at 4-5 degrees C.

Aztreonam↗
PubMed1984

[Sensitizing action of nonvirion admixtures in inactivated influenza vaccines in an experiment].

The side-effect of nonvirion admixtures in inactivated influenza vaccines has been experimentally studied. The minimal sensitizing dose of allantoic admixtures other than ovalbumin has been experimentally determined in vivo. This dose has proved to be 4 times higher than the sensitizing dose of ovalbumin. The presence of sharply defined correlations between the concentration of the admixtures contained in inactivated influenza vaccines, the titers of antibodies to these admixtures and the severity of anaphylactic reactions has been established in guinea pigs after their multiple immunization.

Allantois↗
PubMed1978

Intropin (dopamine hydrochloride) intravenous admixture compatibility, Part 3: stability with miscellaneous additives.

The compatibility of dopamine hydrochloride (Intropin) with various additives in 5% Dextrose Injection, USP, was studied. Dopamine hydrochloride stability for 24 hours in the admixture was established by colorimetric and thin-layer chromatographic procedures. Dopamine hydrochloride solutions are generally stable at an acidic pH and all admixtures produced a slightly acidic solution. Additives tested and found stable for 24 hours in the presence of Intropin included heparin sodium, lidocaine hydrochloride, neutral cephalothin sodium, oxacillin sodium and gentamicin sulfate. The chemical stability of methylprednisolone sodium succinate and hydrocortisone sodium succinate was not established. Potassium chloride, calcium chloride and calcium gluceptate may be assumed to be stable in the presence of Intropin. Above pH 5.0, the calcium gluceptate-Intropin admixture exhibited a color change indicating physical incompatibility. The pH and physical compatibility of all admixtures were established. 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 Intropin.

Dopamine↗
PubMed1982

Microbiologic quality assurance for intravenous admixtures in a small hospital.

A simple, inexpensive method for end-product testing of intravenous admixtures for microbial contamination was developed and tested by challenging the system with low levels of microbial contamination. The 16-step procedure for testing i.v. admixtures for microbial contamination used total-sample membrane filtration A 0.2-micrometers Nalgene filter unit was used; the entire contents of randomly selected admixtures were to be filtered and discarded under the procedure. Filters were incubated on sheep-blood agar plates for 48 hours at 35 degrees C. Low concentrations (Klebsiella pneumoniae and Pseudomonas aeruginosa were used to contaminate admixtures deliberately to challenge the system. Seventy-two solutions were contaminated with each microbe; 72 other solutions were inoculated with sterile 0.9% sodium chloride; and 72 uninoculated solutions served as controls. Filtration was performed on a laboratory bench to prevent contamination of the laminar-flow hood. In deliberately contaminated solutions, a mean of 82% of inoculated organisms was isolated by membrane filtration. Five instances of adventitious contamination were noted among the 288 samples; these occurred across all experimental groups. Cost per sample was $4-5. This system can be used by hospital pharmacists to produce documentation of quality assurance that will be acceptable in terms of cost, simplicity, and accuracy.

Drug Compounding↗
PubMed1982

Word-processing system in a centralized intravenous admixture program.

The application of a word-processing system to a centralized i.v. admixture service is described. The pharmacy department of a 560-bed private hospital developed its admixture service with a limited increase in staff and without compromising its clinical services by using a commercially available word-processing system. The system allows the user to type, edit, store, and print patient profiles and labels for total parenteral nutrition solutions, i.v. piggyback medications, and large-volume parenterals. The data for the admixture service are stored in three diskettes--one for piggybacks, one for TPNs, and one for other applications. Operational details regarding all applications are described. The word-processing system provides a relatively inexpensive method of coping with the large amount of data manipulation and label preparation inherent in a sophisticated i.v. admixture program.

Centralized Hospital Services↗
PubMed1983

Premixed intravenous admixtures: a critical challenge for hospital pharmacy.

The advantages and disadvantages of premixed intravenous admixtures are discussed in the context of their effects on hospital pharmacy practice. Premixed i.v. admixtures offer the advantages of preparation-time savings, assurance of properly reconstituted drugs, lengthy expiration dating, and appropriate labeling. However, because not all drugs will be available from all three i.v. solution manufacturers, hospitals may be forced to use several types of i.v. containers and administration sets. Storage-space requirements will be increased, as the pharmacy will need to stock both premixed and unmixed products. Health-care personnel may be confused about whom to call (the drug manufacturer or the i.v. manufacturer) for drug information on premixed admixtures. Quantity discounts will likely decrease as fewer base i.v. solutions and unmixed drug products are purchased. Plans should be made now to shift personnel from admixture preparation to clinically oriented programs and to develop new workload indicators for pharmacy departments.

Drug Combinations↗
PubMed1983

Premixed intravenous admixtures: a positive development for hospital pharmacy.

The development of premixed intravenous admixtures is reviewed in a historical context, and its effects on hospital pharmacy practice are discussed. As pharmaceutical manufacturers introduce more i.v. medications in ready-to-use containers, the same complaints that were voiced by pharmacists about unit dose packaging and ready-to-dispense tablets and capsules are being aired. But premixed i.v. admixtures are a logical extension of the basic unit dose principle of providing a readily identifiable and ready-to-administer dose. The time and cost savings these products offer are needed in hospital pharmacies. Some of the disadvantages of these products--including storage and freezer space and multiplicity of administration systems--are overcome by proper planning and education of personnel. If fewer personnel are now needed to prepare i.v. admixtures, then those personnel should be used to improve patient care in other ways. The use of premixed i.v. admixtures is a positive technological advance in drug packaging. Its advantages outweight its disadvantages, and it will soon be become the universally accepted form of i.v. drug packaging.

Drug Combinations↗
PubMed1981

Stability and sterility of cimetidine admixtures frozen in minibags.

The stability and sterility of cimetidine hydrochloride admixtures after freezing for extended periods were investigated. Cimetidine hydrochloride, 300 mg, was added to each of six 50-ml minibags containing 5% dextrose injection. The cimetidine concentration was determined and the bags were frozen for up to 30 days. After freezing for the appropriate length of time, the bags were thawed. Cimetidine concentrations were determined by high-pressure liquid chromatography immediately and then daily for eight days while the admixtures were refrigerated. Sterility tests were carried out throughout the study. Data were analyzed by least-squares linear regression to test for trends. The cimetidine hydrochloride admixtures were stable while frozen for up to 30 days and for at least eight days following thawing when kept under refrigeration. Sterility of the admixture was maintained throughout the study period.

Cimetidine↗
PubMed1995

The transmission/disequilibrium test: history, subdivision, and admixture.

Disease association with a genetic marker is often taken as a preliminary indication of linkage with disease susceptibility. However, population subdivision and admixture may lead to disease association even in the absence of linkage. In a previous paper, we described a test for linkage (and linkage disequilibrium) between a genetic marker and disease susceptibility; linkage is detected by this test only if association is also present. This transmission/disequilibrium test (TDT) is carried out with data on transmission of marker alleles from parents heterozygous for the marker to affected offspring. The TDT is a valid test for linkage and association, even when the association is caused by population subdivision and admixture. In the previous paper, we did not explicitly consider the effect of recent history on population structure. Here we extend the previous results by examining in detail the effects of subdivision and admixture, viewed as processes in population history. We describe two models for these processes. For both models, we analyze the properties of (a) the TDT as a test for linkage (and association) between marker and disease and (b) the conventional contingency statistic used with family data to test for population association. We show that the contingency test statistic does not have a chi 2 distribution if subdivision or admixture is present. In contrast, the TDT remains a valid chi 2 statistic for the linkage hypothesis, regardless of population history.

Alleles↗
PubMed2025

Admixture-mapping analysis reveals genetic determinants of the human plasma proteome.

Protein profiling and genetic findings can be integrated to define the genetic architecture of the circulating proteome in chronic diseases. Most self-identified African American (AA) individuals have both African and European genetic ancestry. Admixture mapping can detect genomic association regions in which causal variants exist with substantial differences in allele frequency or effect sizes between genetic ancestries. We performed admixture mapping of the circulating proteome in 1,989 participants from the Jackson Heart Study (JHS), investigating the relation of local African ancestry within genomic regions with levels of circulating proteins. We conditioned protein-local ancestry association models on variants previously found to be associated with those proteins in genome-wide association studies (GWASs). We replicated findings in 196 AA participants from the Multi-Ethnic Study of Atherosclerosis (MESA). 62 proteins were associated with local African ancestry. 21 of 62 remained statistically significant after conditioning on protein-associated variants observed in previous GWASs. 48 of 54 available protein-local ancestry associations were replicated in the MESA. Proteins associated with local African ancestry included chemokines, factors associated with vascular biology and inflammation, and other biologically interesting proteins. Admixture associations unexplained by previously reported protein-associated variants in conditional analysis suggest the existence of causal variants missed by standard GWAS techniques.

Aged↗
PubMed2025

Peruvian Population Genomics: Unraveling the Genetic Landscape and Admixture Dynamics of Urban Populations.

Latin American populations exhibit high genetic and phenotypic diversity shaped by complex admixture histories, yet remain underrepresented in genomic research. Here, we analyze genome-wide data from 432 urban individuals across 13 regions of Peru, including 346 newly genotyped from the Peruvian Genome Project. We revealed fine-scale population structure and demographic patterns shaped by both ancient and recent events. Indigenous American ancestries in urban individuals trace back to ancient north-south interactions consisted with archaeological records, while admixture events occurring within the last 8-10 generations involved sources already admixed between distinct ancestral lineages. Identity-by-descent analyses reveal sustained gene flow in southern Peru, while effective population size trends highlight demographic stability in Lima over the past 25 generations. Sex-biased admixture patterns suggest Indigenous ancestry contribution preferentially mediated by females. These findings offer a comprehensive view of Peru's genetic heritage, advancing our understanding of human genetic diversity and historical demographic processes in Latin America.

Admixture↗
PubMedDate not supplied

Maximum likelihood estimates of admixture in Northeastern Mexico using 13 short tandem repeat loci.

Tetrameric short tandem repeat (STR) polymorphisms are widely used in population genetics, molecular evolution, gene mapping and linkage analysis, paternity tests, forensic analysis, and medical applications. This article provides allelic distributions of the STR loci D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820, CSF1PO, TPOX, TH01, and D16S539 in 143 Mestizos from Northeastern Mexico, estimates of contributions of genes of European (Spanish), American Indian and African origin in the gene pool of this admixed Mestizo population (using 10 of these loci); and a comparison of the genetic admixture of this population with the previously reported two polymorphic molecular markers, D1S80 and HLA-DQA1 (n = 103). Genotype distributions were in agreement with Hardy-Weinberg expectations (HWE) for almost all 13 STR markers. Maximum likelihood estimates of admixture components yield a trihybrid model with Spanish, Amerindian, and African ancestry with the admixture proportions: 54.99% +/- 3.44, 39.99% +/- 2.57, and 5.02% +/- 2.82, respectively. These estimates were not significantly different from those obtained using D1S80 and HLA-DQA1 loci (59.99% +/- 5.94, 36.99% +/- 5.04, and 3.02% +/- 2.76). In conclusion, Mestizos of Northeastern Mexico showed a similar ancestral contribution independent of the markers used for evolutionary purposes. Further validation of this database supports the use of the 13 STR loci along with D1S80 and HLA-DQA1 as a battery of efficient DNA forensic markers in Northeastern Mestizo populations of Mexico.

Genetic Markers↗
PubMed1975

Papago Indian admixture and mating patterns in a mining town: a genetic cauldron.

Problems of delineation of population units and sub-units and the poor fit of genetic models make populations with high mobility and low stability difficult to analyze by present means. Examination of three processes īn-migration, admixture, and dispersal as well as the mate selection factors involved in out-mating and changing population boundaries are suggested as alternate procedures in these cases. The Papago Indian community of Ajo, Arizona, is characterized by historical instability, an in-migration rate of 72.3%, a dispersal rate of 20.6%, and an admixture rate of 36.7%. In-migrant parents continue to come from all parts of the reservation, reservation ties are strong, and families often fragmented between reservation and Ajo homes. For these and other reasons the community cannot be delineated as a population unit nor incorporated into models of subdivided populations. Ajo's function as a cauldron in which genes are mixed and from which they are scattered is evident in sharp increases in the percentage of mixed Papagos among residents and out-migrants. Among the latter more than twice as many mixed Papago leave Ajo as entered in the parental generation. Mate selection factors possibly involved in admixture are considered.

Adolescent↗