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PubMed1999

Efficiency of enterohepatic circulation, its determination and influence on drug bioavailability.

A new approach has been developed to determine the factors that influence the balance of drug elimination from the body. This approach is based on 1. a six-compartment-model with compartments connected by different flow rates assuming kinetic processes of first order, 2. on solutions of geometric series and 3. on numerical solutions of a system of non-linear equations. In the model, different ways of drug elimination have been considered: renal, liver and fecal elimination of the drug and its metabolism in the liver. The organs have been characterized by their drug availabilities. Further, the metabolic activity of the liver, the efficiency of drug absorption and re-absorption from the gastrointestinal (GI) tract have been included. This paper identifies three events, characterized by their efficiencies--1. hepatic excretion, 2. elimination of drug from liver into the gall bladder in its non-metabolized form and 3. the re-absorption of the drug from GI tract--as necessary conditions of enterohepatic circulation of (EHC). The product of these efficiencies has been introduced as the efficiency of enterohepatic circulation. Further, the drug bioavailability as a function of the efficiency of EHC is presented. The study shows that--based on the total amounts of non-metabolized drug in urine after p.o. and i.v. administration to animals with and without cannulated bile duct and in the bile of cannulated animals--the efficiency of EHC, bioavailability of the drug, renal and hepatic availability of the drug, metabolic activity of the liver and efficiency of drug absorption and re-absorption from the gut can be determined. Additionally, it has been shown that, depending on the efficiency of enterohepatic circulation, small variabilities in drug pharmacokinetic properties can cause high variance of drug bioavailability. The publication points towards the efficiency of EHC as on a factor that plays a key role in establishing in vitro-in vivo correlation.

Algorithms↗

PubMed1989

Predictions of thermodynamic efficiency in a pumped biochemical reaction.

We propose and analyze a possible experimental system for the investigation of the thermodynamic efficiency of generating biochemical gradients. We investigate the efficiency of a model pump that uses 6-phosphofructokinase (EC 2.7.1.11, an enzyme that exhibits highly nonlinear kinetics), chromatophores from Rhodobacter sphaeroides, and light to generate a biochemical gradient. We analyze the experimental system and an equivalent alternative configuration and show that the establishment and maintenance of a concentration gradient across a membrane is thermodynamically equivalent to the establishment and maintenance of a stationary state in a single-phase, isothermal, open, homogeneous reaction system. With a constant input of light, the system can exist in a stable node (a stable steady state), a stable focus (upon perturbation from its steady state, the system returns to its steady state with an oscillatory component), and a stable limit cycle (at steady state the system exhibits stable oscillations). We investigate the efficiency of the system with both steady and oscillatory light input and observe efficiency changes that depend upon the autonomous state of the system and the frequency and amplitude of the periodic light input. When the system is in a stable focus, an efficiency maximum is seen when the system is perturbed at its resonant frequency. When the system is in a stable limit cycle, efficiency increases are seen near the 1:3, 1:2, and 2:1 entrainment regions and an efficiency decrease is seen near the 1:1 entrainment region. We further calculate various contributions to the efficiency: the phase shift of the force and flux, the magnitude of the response to the perturbation, and changes in the average values of the force and flux during a perturbation. We show that all three changes contribute to the overall changes in efficiency, but increases and decreases in the average force make the largest contributions.

Kinetics↗

PubMed2002

Methods for estimating the transfer efficiency of a compressed air spray gun.

The transfer efficiency of a compressed air spray gun is an important performance index with regard to worker health, environmental, and economic considerations. It is defined as the fraction of paint sprayed that coats the surface. Worker exposure has been identified as a function of the transfer efficiency based on total mass of paint sprayed, which can be predicted by a mathematical model developed with nonvolatile oil. This study extends the existing model to include volatile effects by employing a mathematical approach based on a mass balance. This method allows the current model to predict transfer efficiency bounds at two extreme situations: all volatile compounds evaporate either before or after droplet impaction. Model predictions show that tight transfer efficiency bounds are obtained, especially for high values of transfer efficiency. Thus, the average of the upper and lower bounds should be a reasonable estimate of transfer efficiency. It is also found that the current model prediction, which is based on total mass of paint sprayed, for nonvolatile material can be converted to a transfer efficiency based on the mass of solids. The laboratory study shows that the predicted transfer efficiency based on the mass of solids is within the 95 percent C.I. of the measured value. This work relates the transfer efficiency used in industry, which is calculated on the basis of paint solids, with a model that predicts worker exposure during spray painting operations.

Air Movements↗

PubMed1989

"Worst case" aerosol testing parameters: I. Sodium chloride and dioctyl phthalate aerosol filter efficiency as a function of particle size and flow rate.

The efficiency of filter media is dependent on the characteristics of the challenge aerosol and the filter's construction. Challenge aerosol parameters, such as particle size, density, shape, electrical charge, and flow rate, are influential in determining the filter's efficiency. In this regard, a so-called "worst case" set of conditions has been proposed for testing respirator filter efficiency in order to ensure wearer protection. Data collected on various types of filters (dust and mist; dust, fume, and mist; paint, lacquer, and enamel mist; and high efficiency) challenged with a worst case-type sodium chloride (NaCl) and dioctyl phthalate (DOP) aerosol are presented. The particle size of maximum penetration varies as a function of filter type and was less than 0.25-micron count mean diameter (CMD) in all cases. The count efficiency for high efficiency filters was greater than 99.97% at worst case testing conditions, but the worst case count efficiencies for dust and mist; dust, fume and mist; and paint, lacquer and enamel mist filters were not nearly as efficient as existing test methods indicate. Also, as the test flow rate is increased, the count efficiency decreases. Thus, respirator filters were found to conform to the prediction of single-fiber filtration theory.

Aerosols↗

PubMed2003

Efficiency of onco-retroviral and lentiviral gene transfer into primary mouse and human B-lymphocytes is pseudotype dependent.

B lymphocytes are attractive targets for gene therapy of genetic diseases associated with B-cell dysfunction and for immunotherapy. Transduction of B lymphocytes was evaluated using green fluorescent protein (GFP)-encoding onco-retroviral and HIV-derived lentiviral vectors which were pseudotyped with ecotropic, amphotropic or vesicular stomatitis virus (VSV-G) envelopes. Transduction of mouse B lymphocytes activated with lipopolysaccharides (LPS) or by cross-linking CD40 in conjunction with interleukin-4 (IL-4) was significantly more efficient (p < 0.003) with ecotropic (11%) than with VSV-G pseudotyped onco-retroviral vectors (1%). Using high-titer cell-free ecotropic viral supernatant or by coculture with ecotropic onco-retroviral vector-producing cells, transduction efficiency increased significantly (p < 0.001) to approximately 50%, whereas transduction efficiency by coculture with VSV-G pseudotyped vector-producing cells remained low (< 2%). Similarly, transduction of mouse B lymphocytes was significantly more efficient (twofold, p < 0.01) with the ecotropic (7%) than with the VSV-G pseudotyped lentiviral vectors although gene transfer efficiency remained low because of dose-limiting toxicity of the concentrated vector preparations on the LPS-activated murine B cells. Consistent with murine B-cell transduction, human B cells activated with CD40L and IL-4 were also found to be relatively refractory to VSV-G pseudotyped onco-retroviral vectors (< 1%). However, higher transduction efficiencies could be achieved in activated primary human B lymphocytes using VSV-G pseudotyped lentiviral vectors instead (5%-6%). Contrary to the significant increase in mouse B-cell transduction efficiency with ecotropic vectors, the use of amphotropic onco-retroviral or lentiviral vectors did not increase transduction efficiency in primary human B cells. The present study shows that the transduction efficiency of onco-retroviral and lentiviral vectors in human and mouse B lymphocytes is pseudotype-dependent and challenges the widely held assumption that VSV-G pseudotyping facilitates gene transfer into all cell types.

Animals↗

PubMed2004

Breeding for high water-use efficiency.

There is a pressing need to improve the water-use efficiency of rain-fed and irrigated crop production. Breeding crop varieties with higher water-use efficiency is seen as providing part of the solution. Three key processes can be exploited in breeding for high water-use efficiency: (i) moving more of the available water through the crop rather than it being wasted as evaporation from the soil surface or drainage beyond the root zone or being left behind in the root zone at harvest; (ii) acquiring more carbon (biomass) in exchange for the water transpired by the crop, i.e. improving crop transpiration efficiency; (iii) partitioning more of the achieved biomass into the harvested product. The relative importance of any one of these processes will vary depending on how water availability varies during the crop cycle. However, these three processes are not independent. Targeting specific traits to improve one process may have detrimental effects on the other two, but there may also be positive interactions. Progress in breeding for improved water-use efficiency of rain-fed wheat is reviewed to illustrate the nature of some of these interactions and to highlight opportunities that may be exploited in other crops as well as potential pitfalls. For C3 species, measuring carbon isotope discrimination provides a powerful means of improving water-use efficiency of leaf gas exchange, but experience has shown that improvements in leaf-level water-use efficiency may not always translate into higher crop water-use efficiency or yield. In fact, the reverse has frequently been observed. Reasons for this are explored in some detail. Crop simulation modelling can be used to assess the likely impact on water-use efficiency and yield of changing the expression of traits of interest. Results of such simulations indicate that greater progress may be achieved by pyramiding traits so that potential negative effects of individual traits are neutralized. DNA-based selection techniques may assist in such a strategy.

Agriculture↗

PubMed1985

Efficiency estimation for detecting U alpha particles in solid-state nuclear track detectors.

The detection efficiencies of solid-state nuclear track detectors, made with cellulose nitrate materials (LR-115 II) or allyl diglycol carbonate (CR-39) were investigated. Detection efficiency for a surface alpha source was experimentally obtained by changing the dimensions between the detector and the source, while alpha-particle incident efficiency was calculated. The ratio of the detection efficiency to the incident efficiency was then determined. It was confirmed that the ratio for LR-115 II was dependent on energy, but for CR-39 the ratio showed almost no dependency. Considering the relationship between solid absorber thickness and detection efficiency of the surface alpha source, detection efficiencies of U in various metals were estimated. The efficiency for U contained in Al and Fe was proposed as 16% for LR-115 II and 22% for CR-39. Using these efficiencies, amounts of U in some Al and Fe ingots were determined. These agreed with concentrations obtained by neutron-activation analysis with deviations of less than 15%.

Alpha Particles↗

PubMed2003

An experimental determination of FIDLER scanning efficiency at specific speeds.

As part of mass remediation efforts across the country some radiation detection systems are now being used in conjunction with data logging and positioning system technology. These systems can be used in the scanning mode, simultaneously recording both count rate and position. Following data analysis, hot spots can be identified and remediation efforts for that particular area can commence. This technique has been used for nearly a decade and has had success in accelerating preliminary remediation work while also reducing potential clean up costs. However, little work has been completed on how the sensitivity of these detection systems are affected when used with this technology because while the intrinsic efficiency of the detector is constant, scanning efficiency can vary depending on data sampling time and scanning speed. To better understand scanning efficiency for a detector attached to such a system, a device was developed which moved soil at a constant speed underneath a Field Instrument for Detecting Low Energy Radiation (FIDLER). Count rate was measured every 2 s as a 241Am source passed under the detector at speeds ranging from approximately 10 cm s(-1) to 100 cm s(-1). A surface source and a buried source were both examined. Experimental detection efficiency was calculated and compared to Monte Carlo generated results. For the surface source, the efficiency dropped to a value of approximately 1% at 100 cm s(-1). At the same speed, the buried source had a detection efficiency of 0.1%, primarily due to attenuation of the low energy photon in the soil. It was also noted that the response time of the meter affected the scanning efficiency. With a response time set at 1 s, higher average efficiencies were recorded but with a large standard deviation from the mean. Higher response time setting had the effect of reducing the variability of the reading but also reducing efficiency.

Americium↗

PubMed1997

Ventriculoarterial coupling and left ventricular efficiency in heart transplant recipients.

BACKGROUND: In heart transplants, left ventricular function may be impaired in the absence of rejection or graft atherosclerosis. Matching between left ventricle and arterial receptor, i.e., ventriculoarterial coupling, and left ventricular efficiency have never been studied. METHODS: Left ventricular pressure-volume loops and single beat analysis were used to determine effective arterial elastance (Ea) and the slope of the end-systolic pressure-volume relation (end-systolic elastance; Ees). Left ventricular efficiency was evaluated by determination of external work (EW), pressure-volume area (PVA), coronary blood flow (continuous thermodilution), and myocardial oxygen consumption (MVO2). Measurements were made at baseline in 11 control subjects and 9 heart transplant recipients (HTX) without rejection and were repeated after phenylephrine in the latter group. RESULTS: At baseline, Ees, Ees/Ea, and work efficiency (EW/PVA) were lower in HTX than in control subjects (2.51+/-0.87 vs. 3.70+/-1.15 mmHg/ml/m2, P<0.01; 0.96+/-0.21 vs. 1.47+/-0.31, P<0.001; and 0.53+/-0.08 vs. 0.59+/-0.09, P<0.01, respectively). Energy conversion efficiency (PVA/MVO2) and mechanical efficiency (EW/ MVO2) were higher in HTX (0.58+/-0.08 vs. 0.45+/-0.14, P<0.001; and 0.31+/-0.05 vs. 0.26+/-0.06, P<0.001, respectively). In HTX, phenylephrine infusion increased Ees, Ea, EW, PVA, and MVO2 without modifying Ees/Ea, EW/PVA, PVA/MVO2, and EW/MVO2. CONCLUSIONS: In heart transplants, (1) left ventricular contractility is moderately depressed; (2) elevation of energy conversion efficiency compensates for the decrease in work efficiency, allowing normal mechanical efficiency; and (3) alpha 1 adrenergic stimulation does not impair ventriculoarterial coupling and mechanical efficiency.

Adult↗

PubMed2001

The role of nitrogen-efficient cultivars in sustainable agriculture.

To improve nitrogen (N) efficiency in agriculture, integrated N management strategies that take into consideration improved fertilizer, soil, and crop management practices are necessary. This paper reports results of field experiments in which maize (Zea mays L.) and oilseed rape (Brassica napus L.) cultivars were compared with respect to their agronomic N efficiency (yield at a given N supply), N uptake efficiency (N accumulation at a given N supply), and N utilization efficiency (dry matter yield per unit N taken up by the plant). Under conditions of high N supply, significant differences among maize cultivars were found in shoot N uptake, soil nitrate depletion during the growing season, and the related losses of nitrate through leaching after the growing season. Experiments under conditions of reduced N supply indicated a considerable genotypic variation in reproductive yield formation of both maize and oilseed rape. High agronomic efficiency was achieved by a combination of high uptake and utilization efficiency (maize), or exclusively by high uptake efficiency (rape). N-efficient cultivars of both crops were characterized by maintenance of a relatively high N-uptake activity during the reproductive growth phase. In rape this trait was linked with leaf area and photosynthetic activity of leaves. We conclude that growing of N-efficient cultivars may serve as an important element of integrated nutrient management strategies in both low- and high-input agriculture.

Agriculture↗

PubMed2002

Transformation of the cyanobacterium Synechocystis sp. PCC 6803 as a tool for genetic mapping: optimization of efficiency.

The cyanobacterium Synechocystis sp. PCC 6803 is transformable at high efficiency and integrates DNA by homologous double recombination. However, several genetic mapping procedures depend on the ability to generate transformants even with very small amounts of added DNA. This study is aimed at optimizing the transformation efficiency at limiting concentrations of exogenous DNA. The transformation efficiency showed little sensitivity to experimental conditions. Transformation with circular plasmid DNA was found to be no more than 30% more efficient than with linearized plasmid DNA. The efficiency of transformation remained essentially the same in the presence of competing DNA, indicating that the capacity of DNA uptake by the cells is not limiting. The incubation time of cells with DNA before plating (0-8 h) affected the transformation efficiency by up to 3-fold. Only minor changes in the efficiency were observed as a function of the presence of a membrane filter on the plate or the presence of TAE or TBE gel buffer residues in the transformation mixture. However, transformability of the host strain of Synechocystis sp. PCC 6803 was increased by two orders of magnitude if the sll1354 gene encoding the exonuclease RecJ was deleted. Therefore, the transformation efficiency of Synechocystis sp. PCC 6803 with exogenous DNA appears to be determined primarily by intracellular processes such as the efficiency of DNA processing and homologous recombination.

Bacterial Proteins↗

PubMed1996

Mechanical efficiency and fatigue of fast and slow muscles of the mouse.

1. In this study, the efficiency of energy conversion in skeletal muscles from the mouse was determined before and after a series of contractions that produced a moderate level of fatigue. 2. Initial mechanical efficiency was defined as the ratio of mechanical power output to the rate of initial enthalpy output. The rate of initial enthalpy output was the sum of the power output and rate of initial heat output. Heat output was measured using a thermopile with high temporal resolution. 3. Experiments were performed in vitro (25 degrees C) using bundles of fibres from fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles from mice. Muscles were fatigued using a series of thirty isometric tetani. Initial mechanical efficiency was determined before and again immediately after the fatigue protocol using a series of isovelocity contractions at shortening velocities between 0 and the maximum shortening velocity (Vmax). Efficiency was determined over the second half of the shortening at each velocity. 4. The fatigue protocol significantly reduced maximum isometric force Vmax, maximum power output and flattened the force-velocity curve. The magnitude of these effects was greater in EDL muscle than soleus muscle. In unfatigued muscle, the maximum mechanical efficiency was 0.333 for EDL muscles and 0.425 for soleus muscles. In both muscle types, the fatiguing contractions caused maximum efficiency to decrease. The magnitude of the decrease was 15% of the pre-fatigue value in EDL and 9% in soleus. 5. In a separate series of experiments, the effect of the fatigue protocol on the partitioning of energy expenditure between crossbridge and non-crossbridge sources was determined. Data from these experiments enabled the efficiency of energy conversion by the crossbridges to be estimated. It was concluded that the decrease in initial mechanical efficiency reflected a decrease in the efficiency of energy conversion by the crossbridges.

Animals↗

PubMed2002

Monte Carlo study of a highly efficient gas ionization detector for megavoltage imaging and image-guided radiotherapy.

The imaging characteristics of an arc-shaped xenon gas ionization chamber for the purpose of megavoltage CT imaging were investigated. The detector consists of several hundred 320 microm thick gas cavities separated by thin tungsten plates of the same thickness. Dose response, efficiency and resolution parameters were calculated using Monte Carlo simulations. The calculations were compared to measurements taken in a 4 MV photon beam, assuming that the measured signal in the chambers corresponds to the therein absorbed dose. The measured response profiles for narrow and broad incident photon beams could be well reproduced with the Monte Carlo calculations. They show, that the quantum efficiency is 29.2% and the detective quantum efficiency at zero frequency DQE(0) is 20.4% for the detector arc placed in focus with the photon source. For a detector placed out of focus, these numbers even increase. The efficiency of this kind of radiation detector for megavoltage radiation therefore surpasses the reported efficiency of existing detector technologies. The resolution of the detector is quantified with calculated and measured line spread functions. The corresponding modulation transfer functions were determined for different thicknesses of the tungsten plates. They show that the resolution is only slightly dependent on the plate thickness but is predominantly determined by the cell size of the detector. The optimal plate thickness is determined by a tradeoff between quantum efficiency, total signal generation and resolution. Thicker plates are more efficient but the total signal and the resolution decrease with plate thickness. In conclusion, a gas ionization chamber of the described type is a highly efficient megavoltage radiation detector, allowing to obtain CT images with very little dose for a sufficient image quality for anatomy verification. This kind of detector might serve as a model for a future generation of highly efficient radiation detectors.

Animals↗

PubMed1973

Integration efficiencies of spontaneous mutant alleles of amiA locus in pneumococcal transformation.

The distribution of integration efficiencies of independent mutations spontaneously occurring in the amiA locus was determined in two strains of pneumococcus. Strain Cl(3) integrates genetic markers with different efficiencies during transformation, whereas strain 401, isogenic with strain Cl(3), does not discriminate between markers and integrates all markers with the same high efficiency. The discriminating strain Cl(3) gives rise to spontaneous mutations in the locus amiA, which fall into four classes with respect to their individual integration efficiencies. Mutations with a low efficiency of integration are equal in number to mutations with a high efficiency. Mutations from the two other classes corresponding to intermediate and very high efficiencies are about five times less frequent. The same four classes were also found among amiA mutants spontaneously occurring in strain 401. However, the two distributions of integration efficiencies of amiA mutants arisen either in strain Cl(3) or strain 401 are significantly different. The number of spontaneous amiA mutants, estimated by two methods, was found to be higher in strain 401 than in strain Cl(3). The increase of the mutation rate in strain 401 could be accounted for by the excess of mutations falling in the two less-efficient classes observed in this strain. The discriminating process which acts during transformation presumably also intervenes in the appearance of spontaneous mutations.

Alleles↗

PubMed2006

Cellular stress rather than stage of the cell cycle enhances the replication and plating efficiencies of herpes simplex virus type 1 ICP0- viruses.

This lab reported previously that the plating efficiency of a herpes simplex virus type 1 ICP0-null mutant was enhanced upon release from an isoleucine block which synchronizes cells to G1 phase (W. Cai and P. A. Schaffer, J. Virol. 65:4078-4090, 1991). Peak plating efficiency occurred as cells cycled out of G1 and into S phase, suggesting that the enhanced plating efficiency was due to cellular activities present in late G1/early S phase. We have found, however, that the enhanced plating efficiency did not occur when cells were synchronized by alternative methods. We now report that the plating efficiency of ICP0- viruses is not enhanced at a particular stage of the cell cycle but rather is enhanced by specific cellular stresses. Both the plating and replication efficiencies of ICP0- viruses were enhanced as much as 25-fold to levels similar to that of wild-type virus when monolayers were heat shocked prior to infection. In addition to heat shock, UV-C irradiation but not cold shock of monolayers prior to infection resulted in enhanced plating efficiency. We further report that the effect of cellular stress is transient and that cell density rather than age of the monolayers is the primary determinant of ICP0- virus plating efficiency. As both cell stress and ICP0 are required for efficient reactivation from latency, the identification of cellular activities that complement ICP0- viruses may lead to the identification of cellular activities that are important for reactivation from neuronal latency.

Animals↗

PubMed1990

The effect of hyperinflation on respiratory muscle strength and efficiency in healthy subjects and patients with asthma.

We evaluated respiratory muscle strength and efficiency in 15 patients with asthma. There was a significant reduction in mean Plmax (89.3 +/- 4.7 versus 110.5 +/- 9.4 cm H2O, p less than 0.001) and efficiency (2.41 +/- 0.2 versus 4.2 +/- 0.6%, p less than 0.01). This reduction in strength and efficiency was seen only in the male patients. Following bronchodilator, there was a significant increase in Plmax (from 89.3 +/- 4.7 to 96.2 +/- 5.4 cm H2O, p less than 0.005) and efficiency (from 2.41 +/- 0.2 to 3.22 +/- 0.2%, p less than 0.001). There was no correlation between the change in strength and efficiency and the degree of improvement in FEV1 following bronchodilator. However, there was a significant correlation with the fall in lung volume. To determine whether hyperinflation would result in a reduction in respiratory muscle strength and efficiency, we induced a mean increase in end-expiratory lung volume of 0.66 L by applying continuous negative pressure around the chest in 10 healthy individuals. This was associated with a significant fall in Plmax (from 110.5 +/- 9.4 to 100.5 +/- 8.93 cm H2O, p less than 0.001) and efficiency (from 4.2 +/- 0.6 to 2.6 +/- 0.5%, p less than 0.005). The data suggest that the strength and efficiency of the respiratory muscles are reduced in asthmatic males but not in the females. The strength and efficiency of the respiratory muscles improve significantly following bronchodilator, and this improvement is related to reduction in lung volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗

PubMed1999

The efficiency concept in pharmacodynamics.

The classic approach to describe the pharmacological response to a drug is to analyse its concentration-effect relationship, using a variety of possible models such as maximum effect (Emax) models or sigmoid Emax models. The aim of this review is to discuss an alternative way of describing the pharmacological effect in terms of effect per unit of drug concentration, instead of simple effect. This variable is called efficiency, analogous with concepts used in other fields. The pharmacodynamic model for efficiency is derived from the sigmoid Emax model and is dependent on the same parameters. Since the sigmoid Emax model incorporates 'the law of diminishing returns', requiring ever higher concentrations to increase the effect by a given percentage, efficiency is bound to decrease with increasing concentrations. However, as a mathematical consequence of its derivation from the sigmoid Emax model, efficiency also has a maximum value, which can be expressed as a function of the slope factor (s) and drug concentration associated with half the maximum effect (C50), provided that the slope factor is greater than 1. The efficiency concept is potentially applicable to all drugs and particularly useful for those that follow concentration-effect relationships according to Emax or sigmoid Emax models. Most experience has been obtained with loop diuretics, especially with furosemide (frusemide). Slow administration of furosemide, leading to slow excretion of the drug, has been shown, in many studies, to significantly increase the total diuretic effect per amount of drug recovered in urine. In this review, some examples of the applicability of the efficiency concept to other drugs, such as antibacterials, opioids and antineoplastics, are discussed. In addition to pharmacodynamically varying efficiency, other saturable processes, such as the formation of active metabolites and saturable transport, may form a basis for the application of the efficiency concept. The efficiency of a drug dosage may also be influenced by tolerance and counter-regulation produced by the drug. All these factors contribute to schedule dependency. It is concluded that the shape of the time course of drug presentation to its site of action is an independent determinant of overall response. The possibility of adjusting the drug input profile to maximise therapeutic effect per dose and to separate cumulated therapeutic from cumulated adverse effects should be considered in designing administration schedules and in drug development.

Biological Availability↗

PubMed1995

Simulated influence of postweaning production system on performance of different biological types of cattle: III. Biological efficiency.

Methods were developed and incorporated into a previously published computer model to predict ME intake and calculate biological efficiencies in terms of grams of empty BW (EBW) and fat-free matter (FFM) gained/megacalorie of ME consumed from weaning to slaughter. Efficiencies were calculated for steers from F1 crosses of 16 sire breeds (Hereford, Angus, Jersey, South Devon, Limousin, Simmental, Charolais, Red Poll, Brown Swiss, Gelbvieh, Maine Anjou, Chianina, Brahman, Sahiwal, Pinzgauer, and Tarentaise) mated to Hereford and Angus dams, grown under nine backgrounding systems, finished at either a low (1.0 kg) or high (1.36 kg) ADG, and slaughtered at 300 kg carcass weight, small or greater degree of marbling, and 28% carcass fat. Backgrounding systems were high ADG (.9 kg) for 111, 167, or 222 d, medium ADG (.5 kg) for 200, 300, or 400 d, and low ADG (.25 kg) for 300 or 400 d, and 0 d backgrounding. The high ADG finishing system was more biologically efficient than the low ADG finishing system, and generally backgrounding systems were less biologically efficient than direct finishing after weaning (0 d backgrounding). Large-framed breeds were more efficient at the constant carcass weight and carcass fatness end point, and breeds that achieved the marbling end point at low levels of carcass fatness were more efficient at this end point. Some small-framed breeds gained EBW more efficiently but gained FFM less efficiently than some of the large-framed breeds. Variation in efficiency between genotypes was greatest with 0 d backgrounding and decreased in the other backgrounding systems.

Aging↗