Goals, values, and life evaluations at the preretirement stage.
Explore the source record for details and available documents.
Adaptation, Psychological↗
SEARCH · Search PubMed
Results for “Value of Life”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
New H1-receptor antagonists: clinical pharmacology.
The non-sedating, second-generation H1-receptor antagonists such as terfenadine, astemizole, loratadine and cetirizine differ considerably from each other in their pharmacokinetics and pharmacodynamics. They are generally well absorbed when administered orally. They have extremely variable serum elimination half-life values. The maximum antihistaminic effect of these medications occurs several hours later than peak serum concentrations do. The duration of the antihistaminic effect is much longer than would be predicted from the serum elimination half-life values. The relative incidence of anticholinergic and central nervous system adverse effects caused by these medications is similar to that produced by placebo. The introduction of the second-generation H1-receptor antagonists represents a major advance in symptomatic therapy of allergic disorders such as allergic rhinitis and urticaria.
Histamine H1 Antagonists↗
Persistence and leaching of beta-cyfluthrin in alluvial soil of India.
Persistence as affected by rate of application and moisture regimes and leaching of beta-cyfluthrin was studied in alluvial soil under laboratory conditions. The effects of rate of application and moisture regimes on persistence were studied by incubating fortified soil at 0.1, 1.0 and 10.0 mg kg(-1) under air-dry, field capacity and submerged moisture regimes. The initial deposits of 0.09, 1.11 and 10.1 mg kg(-1) dissipated with time and 78.4-100% loss was recorded at 90 days. The half-life values varied from 7.8 to 41.8 days. The rate of dissipation decreased as the rate of application increased under field capacity and submerged conditions. However, under air-dry conditions, the effect was less pronounced, and half-life values showed a reverse trend. Persistence of beta-cyfluthrin under different moisture regimes followed the trend: air-dry > field capacity > submerged. The trend could be attributed to the effect of moisture on number and type of microbes. Leaching was studied in a packed soil column under saturated flow conditions. beta-Cyfluthrin was found to be highly immobile in alluvial soil. No residues were detected in any leachate fraction under the experimental conditions. In column soil, residues were detected at 0-10 cm depth and the major amount (>99%) was recovered from 0-5 cm depth. Although beta-cyfluthrin showed moderate persistence in alluvial soil, the possibility of its leaching to ground water is negligible as a result of its immobility.
Algorithms↗
Pharmacokinetics and metabolism of O-(chloroacetyl-carbamoyl) fumagillol (TNP-470, AGM-1470) in rhesus monkeys.
The metabolic disposition and pharmacokinetics of TNP-470 were investigated in rhesus monkeys following intravenous administration of 5 mg/kg of [3H]-TNP-470. Rapid and extensive metabolism of parent drug to six metabolites occurred as demonstrated by the absence of unchanged drug in plasma and urine at time points as early as 6 min after administration. Substantial, yet variable, plasma levels of M-IV were detected in all three monkeys with a mean Cmax value of 3.54 microM. Five other metabolites, labeled M-I, M-II, M-III, M-V and M-VI, were also detected in biological fluids of monkeys. M-II, M-V and M-VI exhibited similar kinetic profiles with apparent plasma elimination half-life values of 0.91 +/- 0.37, 2.42 +/- 0.13 and 1.19 +/- 0.29 h respectively. In contrast, M-I, M-III and M-IV exhibited much shorter apparent plasma half-life values of 30 min or less. Urinary recovery within 36 h represented only 19.90 +/- 6.09% of the total administered dose. No radioactivity was detected beyond 36 h and during a 15-day sample collection period, suggesting that nonrenal (biliary) elimination of TNP-470 metabolites is a predominant excretion route in nonhuman primates. This study provides the first detailed in vivo analysis of TNP-470 metabolism and disposition using an animal model highly predictive of humans, consistent with the detection of the same TNP-470 metabolites in human tissues. A detailed understanding of TNP-470 metabolism and disposition is critical to fully elucidate the pharmacodynamic properties of this new anticancer drug as clinical investigations proceed.
Animals↗
The effect of chronic administration of hydroxyzine on hydroxyzine pharmacokinetics in dogs.
Subsensitivity to H1-receptor antagonists has been attributed to autoinduction of enzyme systems and increased clearance rates during chronic drug administration. We studied the changes in serum half-life values and clearance rates in dogs who were administered hydroxyzine, 0.7 mg/kg, intramuscularly, daily, for 150 days. Pharmacokinetic studies were performed on the first day of drug administration, and on days 30, 60, 90, 120, and 150. The mean serum half-life value on day 30, 60, and 120 was significantly longer (p less than 0.05) than that of 2.4 +/- 0.3 hours obtained on day 1. The mean clearance values obtained on days 30, 60, 90, 120, and 150 were significantly slower (p less than 0.05) than the value of 25.12 +/- 4.13 ml/min/kg obtained on day 1 but were not significantly different from each other. Mean serum hydroxyzine concentrations were often significantly higher on the later study days than on day 1. The mean apparent volume of distribution values obtained on days 30, 60, 90, 120, and 150 did not differ significantly from the value of 5.0 +/- 1.5 L/kg obtained on day 1. This study adds to the mounting evidence that subsensitivity to the effects of an H1-receptor antagonist is not due to autoinduction of enzyme systems, more rapid clearance of the drug, and lower concentrations of the drug in serum and tissue.
Animals↗
Pharmacokinetic optimisation of histamine H1-receptor antagonist therapy.
Second-generation, relatively nonsedating histamine H1-receptor antagonists (H1-RA) are extensively used worldwide for the symptomatic treatment of allergic rhinoconjunctivitis and chronic urticaria. Information about the pharmacokinetics and pharmacodynamics of these medications, while still incomplete, is now sufficient to permit optimisation of therapy. Published pharmacokinetic and pharmacodynamic information on these H1-RA is summarised here, and areas where more data are required are delineated. Serum concentrations of most second-generation H1-RA are relatively low, and are usually measured by radioimmunoassay. After oral administration, peak concentrations are observed within 2 or 3 h. Bioavailability has not been well studied, due to the lack of intravenous formulations. Most H1-RA are metabolised in the hepatic cytochrome P450 system: terfenadine, astemizole, loratadine, azelastine, and ebastine have 1 or more active metabolites which are present in serum in higher concentrations than the respective parent compound, and therefore can be measured by high performance liquid chromatography. Cetirizine, an active metabolite of the first generation H1-receptor antagonist hydroxyzine, is not further metabolised to any great extent in vivo, and is eliminated via renal excretion. Levocabastine is also eliminated primarily by excretion. Serum elimination half-life values differ greatly from 1 H1-RA to another, and are 24 h or less for terfenadine, astemizole, loratadine, cetirizine, azelastine and ebastine, and the active metabolites of terfenadine, loratadine and ebastine. The active metabolite of azelastine (demethylazelastine) has a serum elimination half-life value of about 2 days, while that of astemizole (demethyl-astemizole) has a value of 9.5 days. From the few published studies in which the apparent volumes of distribution of the second-generation H1-RA have been calculated, it appears that tissue distribution is extensive. In children, the half-lives of H1-RA are generally shorter than are found in adults; there is no published information on the pharmacokinetics of astemizole, loratadine, azelastine, or ebastine in children. In some elderly adults, terfenadine, loratadine and cetirizine may have longer half-lives than in young healthy adults. There is little published data on the pharmacokinetics of the second-generation H1-RA in patients with impaired hepatic function. The half-life of cetirizine is prolonged in those with impaired renal function. There is a paucity of information on the pharmacokinetics of H1-RA in neonates, in pregnancy or during lactation.(ABSTRACT TRUNCATED AT 400 WORDS)
Administration, Oral↗
Pharmacokinetics and pharmacodynamics of ebastine in children.
Ebastine is a new piperidine-containing, relatively nonsedating second-generation H1-receptor antagonist. In a double-blind, parallel-group study of a single 5 mg or 10 mg dose of ebastine syrup used to treat allergic rhinitis in 20 children aged 6 to 12 years, we tested the hypothesis that the medication would have a duration of action of at least 24 hours. We measured plasma concentrations of carebastine, the pharmacologically active metabolite of ebastine, and the wheals and flares produced by epicutaneous tests with histamine phosphate, 1.0 mg/ml. Ebastine was absorbed well; peak carebastine concentrations occurred approximately 3 hours after dosing. Mean plasma elimination half-life values of carebastine ranged from 10 to 14 hours. The pharmacokinetics of carebastine were linear and dose independent in the dosage range studied. After the 5 or 10 mg dose, there were no significant differences between mean plasma elimination half-life values, mean oral clearance values, or mean apparent volumes of distribution. Mean peak plasma carebastine concentrations and mean areas under the plasma carebastine concentration-time curve after the 10 mg dose were 1.93 and 1.76 times, respectively, the values obtained after the 5 mg dose. Both doses significantly reduced the histamine-induced wheal-and-flare areas for up to 28 hours compared with predose values. The differences in effect between the doses generally were not statistically or clinically significant. No adverse effects were noted. We conclude that ebastine, an effective H1-receptor antagonist with a prompt onset of action and a long duration of action, is suitable for once-daily administration to children.
Butyrophenones↗
Half-life of the plasma membrane ATPase and its activating system in resting yeast cells.
The stability of the yeast plasma membrane ATPase and its activating system has been investigated in resting Saccharomyces cerevisiae. The half-life of ATPase in the presence of glucose is about 11 h whereas in the presence of ethanol it is greater than 30 h. In the case of the ATPase activating system half-life values of about 5 and 14 h have been observed, respectively, in the presence of these substrates. These results indicate that, similarly to sugar transport systems, plasma membrane ATPase as well as its activating system are less stable than the bulk of proteins in this organism. The fact that all plasma membrane proteins so far examined show low half-life values suggests that a low stability could be a general characteristic of these proteins.
Adenosine Triphosphatases↗
Effect of the gene dosage of CgammaP2C19 on diazepam metabolism in Chinese subjects.
OBJECTIVE: To determine whether the gene dosage of CYP2C19 affects the metabolism of diazepam and desmethyldiazepam in healthy Chinese subjects. SUBJECTS AND METHODS: Eighteen unrelated adult men were recruited for the study from a total of 101 healthy Chinese volunteers who had been screened for CYP2C19 phenotype and genotype. All subjects received a single oral dose (5 mg) of diazepam, and the pharmacokinetics of diazepam and desmethyldiazepam were compared in six ml homozygotes (ml/ml), six ml heterozygotes (wt/ml), and six wild-type homozygotes (wt/wt). RESULTS: The plasma elimination half-life values of diazepam (84.0 +/- 13.7 hours) and desmethyldiazepam (176.0 +/- 28.9 hours) in subjects of ml/ml were significantly longer than those (62.9 +/- 9.8 hours for diazepam; 132.1 +/- 24.9 hours for desmethyldiazepam; both P < .01) in subjects of wt/ml or those (20.0 +/- 10.8 hours for diazepam; 99.2.+/- 21.7 hours for desmethyldiazepam; both P < .01) in subjects of wt/wt. A significant difference in the corresponding half-life values existed between the wt/ml and wt/wt subjects (P < .01). As expected, the slowest mean clearance of diazepam was observed in the ml/ml subjects (2.8 +/- 0.9 mL/min) and the fastest in the wt/wt subjects (19.5 +/- 9.8 mL/min), with the wt/ml heterozygotes having an intermediate value (7.2 +/- 2.6 mL/min). CONCLUSION: The presence of a single-nucleotide polymorphism (G681A) of the CYP2C19 gene cosegregates with the impaired metabolism of diazepam and desmethyldiazepam among Chinese subjects in a gene-dosage effect manner.
Adult↗
Disposition of methamphetamine and its metabolite amphetamine in brain and other tissues in rats after intravenous administration.
These studies characterized the concentration-time profile of (+)-methamphetamine [(+)-METH] and its metabolite (+)-amphetamine [(+)-AMP] in the brain and five other tissues after (+)-METH administration. Male Sprague-Dawley rats received a pharmacologically active (+)-METH i.v. bolus dose (1.0 mg/kg) or a nonpharmacologically active s.c. infusion (20 h at 1.2 mg/kg/day). Tissues (n = 3 per time point) were collected for more than four elimination half-lives in the i.v. group, or at a single steady-state time point (20 h) in the s.c. group. Based on data from the area under the concentration-time curves after i.v. dosing, the rank order of (+)-METH tissue accumulation was kidney > spleen > brain > liver > heart > serum with terminal elimination half-life values ranging from 53 to 66 min. (+)-METH concentrations were highest at the first measured time point (2 min) in all tissues except the spleen, which peaked at 10 min. The brain-to-serum concentration ratio rose from 7:1 at 2 min to a peak of 13:1 at 20 min before equilibrating to a constant value of 8:1 at 2 h. Following s.c. (+)-METH dosing, the (+)-METH brain-to-serum concentration ratio was the same as the equilibrated ratio following i.v. dosing. (+)-AMP concentrations peaked at 20 min in all tissues before decaying with terminal elimination half-life values ranging from 68 to 75 min. Analysis of the area under the concentration-time curve molar amounts of (+)-AMP and (+)-METH showed that (+)-AMP accounted for approximately one-third of the drug tissue exposure over time. Thus, these data indicate the importance of both (+)-METH and (+)-AMP in pharmacological effects following i.v. (+)-METH administration.
Amphetamine↗
Human toxicokinetics of inhaled monochlorobenzene: latest experimental findings regarding re-evaluation of the biological tolerance value.
OBJECTIVE: The aim of this study was to obtain toxicokinetic data on the absorption and elimination of monochlorobenzene (MCB) in blood and its main metabolite 4-chlorocatechol (4-ClCat) as well as on the isomeric chlorophenols (o-ClPh, m-ClPh, and especially p-CIPh as the main ClPh metabolite) in urine for reevaluation of the biological tolerance (BAT) value of MCB. METHODS: Eight subjects performed 8-h inhalation tests daily over five successive days in an exposure chamber, at a maximum allowable concentration at the workplace (MAK) value of 10 ppm MCB. Five and two probands carried out the test series during physical activity levels of 75 and 50 W, respectively, for 10 min/h on a bicycle ergometer, and one subject was exposed continuously while at rest. MCB and its metabolites were analyzed by gas chromatography in combination with mass spectrometry. RESULTS: The mean MCB blood concentration of the five subjects exposed during physical activity of 75 W was 217 +/- 42 microg/l. The relationship of the mean blood concentration measured under the conditions of rest or 50 and 75 W activity levels was in a ratio of about 1:1.7:2.8. The half-life values in the first hour after ending the exposures were 53 min and 150 min for the ensuing period, with steady-state being reached after 45 min. The mean 4-ClCat concentration in urine at the end of the five days was 150 +/- 13 mg/g creatinine in the case of the subjects exposed at 75 W, which decreased to 25 mg/g creatinine at the beginning of the next exposure. The analogous p-ClPh concentrations were 25 +/- 2 and 9 +/- 2 mg/g creatinine. The elimination half-life values of the ClPh isomers ranged from 12.4 to 16.5 h, and the half-life of 4-ClCat was 6.4 h. There was no apparent tendency for MCB and its metabolites to accumulate in blood or urine. CONCLUSIONS: The results are in accordance with relevant field and laboratory studies. Taken into consideration with the 95th percentile, the evaluated BAT values should be set at levels of 300 microg MCB/l blood, 175 mg 4-ClCat/g creatinine or alternatively at 30 mg p-ClPh/g creatinine in urine after the end of a shift. At the beginning of the next shift, the BAT values of the metabolites should be 35 and 15 mg/g creatinine, respectively.
Adult↗
[Measurement of uteroplacental circulation with 113m indium in diabetic pregnancy].
In 122 diabetic pregnancies the placental blood flow has been estimated determining the half life of the activity inflow (2 MBq 113 m In labelled transferrin) into the placental bed. We used a highly sensitive detector (modified pinhole collimator) and a computer supported evaluation, free from subjective influences. 259 flow measurements were compared to the risk of complication in the course of a diabetic pregnancy. - The half life values in the diabetic group, calculated by a gamma camera computer system by means of an iterative regression analysis, were significantly different compared to a control group (12 pregnancies without risk.) - Severe diabetic angiopathic complications (White classes D, F, and R) are accompanied by higher half life values (placental blood flow reductions) and perinatal complications. - Even in pregnant women with gestational diabetes or disturbances of the carbohydrate metabolism a disturbed placental hemodynamic is to be found.
Adult↗
Correlation of in vivo and in vitro inhibition of thrombin by plasma inhibitors.
Rabbit antithrombin III and thrombin were purified to homogeneity to determine the in vivo relationship of these proteins in an autologous system. These proteins, radiolabeled with Na[125I], were injected into rabbits to determine the circulatory half-life. The mean half-life values were 125I-antithrombin III, 54.75 +/- 3.10 hr; 125I-thrombin, 7.25 +/- 1.49 hr; 125I-thrombin-antithrombin III, 7.25 +/- 1.09 hr; 125I[thrombin-antithrombin III], 11.13 +/- 0.88 hr; and Tos-Lys-CH2Cl-125I-thrombin, 27.75 +/- 3.18 hr. All the mean half-life values were statistically different from that of thrombin alone except for the two forms of thrombin-antithrombin III complex. Following injection of the radiolabeled proteins, plasma samples were obtained and gel-filtered to analyze the molecular weight distribution of the radiolabel. An identical elution position on gel filtration of 125I-antithrombin III with native antithrombin III was observed. The 125I-thrombin distributed into two peaks of radioactivity, with a molecular weight of 100,000 (79%) and a molecular weight greater than 200,000 (21%). The 100,000 dalton peak is consistent with a thrombin--antithrombin III complex, and the greater than 200,000 dalton peak is consistent with a thrombin-alpha 2-macroglobulin complex as confirmed by in vitro immunochemical studies. Thrombin inactivated with Tos-Lys-CH2Cl also showed two peaks of radioactivity on gel filtration, one peak which was excluded from the column and the other peak with an elution volume that was consistent with the position of native thrombin.
Antithrombin III↗
Pharmacokinetics of acipimox and of its N-deoxy metabolite following single and repeated oral administration to healthy volunteers.
The aim of the present study was to evaluate the plasma pharmacokinetics of acipimox and of its N-deoxy metabolite (5-methylpyrazine-2-carboxylic acid, MPCA) following single and repeated administration of 250 mg acipimox (thrice daily, for 6 days) to ten healthy volunteers. Mean maximum concentration, the corresponding time, area under the curve extrapolated to infinity and elimination half-life values of acipimox after single administration were equal to 5.74 micrograms/ml (range 2.56-8.38 micrograms/ml), 1.7 h (1-3 h), 16.99 micrograms/ml.h (11.28-22.17 micrograms/ml.h) and 1.15 h (0.79-1.48 h), respectively. Mean area under the curve over one dosing interval (8 h) and elimination half-life values of acipimox after repeated dosing were not significantly different from the corresponding values after the single dose. No significant accumulation was observed following the repeated treatment, since the mean accumulation ratio was 1.08 (range 0.74-1.52). The mean maximum concentration and corresponding time values in the 7 out of 10 subjects with detectable metabolite levels after the single dose were 0.19 microgram/ml (0.10-0.34 microgram/ml) and 6.7 h (3-12 h), respectively, whilst after the repeated treatment, detectable concentrations of the metabolite were observed in all subjects, the mean maximum concentration value being equal to 0.48 micrograms/ml (0.11-1.19 microgram/ml). The average ratio of the parent/metabolite area under the curve values (8 h) after repeated dosing was equal to 14 (range 2-56). Inter-subject variability in the extent of metabolite formation was very high.
Administration, Oral↗
Effect of amino acid reutilization in the determination of protein turnover in mice.
Using different decay data of "in vivo" pulse-labeled protein, the half-life values of different fractions from mouse liver, heart, striated leg muscle, jejunum and epidydimal fat pads were calculated by considering labeled intracellular amino acid reutilization. This was accomplished by substracting the pool amino acid decay rates from the protein decay rates. The extent of reutilization of these labeled amino acids is considerable as shown by the differences found between the corrected and uncorrected half-life calculations. The half-life values obtained for total protein in liver, striated muscle, heart, duodenum and epidydimal fat pad were: 0.57, 1.81, 2.13, 0.68 and 0.42 days, respectively.
Adipose Tissue↗
Fate of silvex following oral administration to humans.
The fate of silvex [2-(2,4,5-trichlorophenoxy)propionic acid] was defined in seven men and in one woman following oral administration of 1 mg/kg. No adverse effects were observed. Samples of blood plasma, urine, and feces were collected at designated time intervals through 168 hr. Plasma samples were analyzed for silvex only, while samples of urine and feces were analyzed for silvex, silvex conjugate(s), 2,4,5-trichlorophenol, and 2,4,5-trichlorophenol conjugate(s). Apparent first-order kinetics described the biphasic clearance of silvex from plasma and excretion in urine. The half-life values for clearance of silvex from plasma were 4.0 +/- 1.9 and 16.5 +/- 7.3 hr for the initial and terminal phases, respectively. Peak plasma levels of silvex occurred within 2-4 hr after dosage. Within 24 hr after administration, 65% of the administered dose had been excreted in urine. Silvex was excreted in urine as silvex and silvex conjugate(s). The half-life values for excretion of silvex per se in urine were 5.0 +/- 1.8 and 25.9 +/- 6.3 hr for the two phases, respectively. Small amounts (3.2% or less) of silvex and/or silvex conjugate(s) were eliminated in feces. Recovery of silvex and its conjugate(s) in urine and feces through 168 hr ranged from 66.6 to 95.1% of the administered dose, with a mean value and standard deviation of 80.3 +/- 10.5%. In humans, silvex is readily absorbed after ingestion and subsequently readily excreted, predominantly via the urine.
Administration, Oral↗
[Behavior of various blood constituents (glucose, fructose, insulin, lactate, pyruvate, free fatty acids, inorganic phosphate) and half-life of monosaccharides in the plasma after i.v. infusion of glucose, fructose, galactose and invert sugar solutions in ruminants. 2. Studies in cattle].
Monosaccharides were intravenously injected to eight adult heads of cattle, between 380 kg and 670 kg in live weight, to study, in the context of stress endurance, the half-life values of the sugars as well as monosaccharide effects upon concentrations of various blood components. The fructose concentration in the blood plasma went up temporarily following the infusion of glucose solution. Fructose infusion usually caused only little rise of the glucose concentration in blood plasma, with hypoglycaemia occurring quite often towards the end of an experimental period. The half-life values of sugar in blood plasma were between twelve and 29 and those of fructose between ten and 17 minutes. The rate of fructose conversion was higher than that of glucose conversion, but values were identical in some cases. The pyruvate concentration in the blood and the insulin level in blood plasma went up in response to infusion of monosaccharide solutions. Urine excretion of monosaccharides following invert sugar infusion was less than half of that in response to glucose infusion.
Animals↗
The relationship between personality and the symptoms of depressive illness.
The Maudsley Personality Inventory and the Beck Depression Inventory, with additional items to assess depressive functional shift features and outlook on life values, were administered to 100 patients diagnosed as suffering from depressive illness. Patients' scores for questions eliciting information about symptoms assumed to be dependent on personality correlated at substantial and significant levels with N scale scores of the Maudsley Personality Inventory. Similar levels of correlation were found for the added items for assessing life values. Items believed to assess changes in functions independent of personality, such as the features of the Depressive Functional Shift, showed no correlation with either N or E scales of the Maudsley Personality Inventory, while demonstrating a substantial level of correlation with the depression scale. It is concluded that whereas changes in innate biological functions independent of environment are direct indications of the depressive illness process, psychological symptoms of the illness may reflect changes in personality dependent on upbringing, education and cultural background, thereby producing greater variation in this group of psychological symptoms.
Body Weight↗