Clinical Pharmacokinetics of Aspirin

PEDIATRICS ◽  
1978 ◽  
Vol 62 (5s) ◽  
pp. 867-872
Author(s):  
Gerhard Levy
Keyword(s):  
Salicylic Acid ◽  
Steady State ◽  
Plasma Concentration ◽  
The Body ◽  
Elimination Kinetics ◽  
Urine Ph ◽  
Clinical Pharmacokinetics ◽  
Daily Dose ◽  
Time Required ◽  
Clinical Conditions

Aspirin is very rapidly absorbed from the gastrointestinal tract when administered as a solution, and somewhat more slowly when administered in tablets. It is rapidly hydrolyzed in the body to salicylic acid; the plasma concentration of the latter must be maintained within a relatively narrow range to obtain an adequate anti-inflammatory effect and to minimize systemic adverse effects. The two major pathways of salicylate elimination, i.e., formation of salicyluric acid and salicyl phenolic glucurocide, become saturated at relatively low body levels of the drug. Consequently, steady-state ("plateau") salicylate levels increase more than proportionately with increasing daily dose, and the time required to reach steady state increases with increasing daily dose. The renal clearance of salicylic acid increases markedly with increasing urine pH; antacids capable of increasing urine pH can therefore cause a pronounced lowering of steady-state salicylate concentrations under clinical conditions. There are pronounced intersubject differences in salicylate elimination kinetics; dosage must be individualized on the basis of plasma concentration and clinical response. The drug is readily transferred across the placenta and is only slowly eliminated by the newborn infant. The drug is also transferred from mother to nursing infant through the breast milk.

scholarly journals Pharmacokinetics and safety of oral levofloxacin in human immunodeficiency virus-infected individuals receiving concomitant zidovudine.

1997 ◽  
Vol 41 (8) ◽  
pp. 1765-1769 ◽  
Author(s):  
S C Chien ◽  
A T Chow ◽  
M C Rogge ◽  
R R Williams ◽  
C W Hendrix
Keyword(s):  
Human Immunodeficiency Virus ◽  
Steady State ◽  
Plasma Concentration ◽  
The Body ◽  
Maximum Plasma Concentration ◽  
Maximum Plasma ◽  
Cell Counts ◽  
Pharmacokinetic Profiles ◽  
Study Results ◽  
Immunodeficiency Virus

This phase I, double-blind, randomized, placebo-controlled, parallel-design study was conducted to evaluate the safety and pharmacokinetics of levofloxacin in human immunodeficiency virus (HIV)-infected subjects concomitantly receiving a stable regimen of zidovudine (AZT). Sixteen HIV-infected males with CD4-cell counts ranging from 100 to 550 and not experiencing significant AZT intolerance were enrolled. Subjects received levofloxacin (350 mg of levofloxacin hemihydrate) or a placebo (eight subjects per treatment group) as a single oral dose on day 1, multiple doses every 8 h from days 3 to 9, and a single dose on day 10. On days 1 and 10, an AZT dose (100 mg) was administered concurrently with the study drug. In between these doses, AZT was administered according to the regimen used by the subject prior to entering the study up to a maximum of 500 mg/day. Plasma levofloxacin concentrations were monitored for 36 h after levofloxacin dosing on day 1, immediately prior to the morning doses on days 3 to 9, and for 72 h after dosing on day 10. Plasma AZT concentrations were monitored on day 0 for baseline (for 6 h after the AZT dose) and for 4 h after the AZT doses on days 1 and 10. Levofloxacin was rapidly absorbed (time to maximum plasma concentration, approximately 1.0 h) and extensively distributed in the body with an apparent volume of distribution of approximately 104 liters (approximately 1.34 liters/kg). Steady-state conditions on day 10 were confirmed. Pharmacokinetic profiles of levofloxacin from single doses and multiple (three-times-daily) doses were similar, with a moderate accumulation (observed day 10-to-day 1 ratio of the maximum plasma concentration, approximately 185% versus expected 169%; for the corresponding ratio of the area under the concentration-time curve from 0 to 8 h [AUC(0-8)], the values were observed 217% versus expected 169%) at steady state. Mean average steady-state peak plasma concentration, plasma levofloxacin concentration at the end of the dosing interval, AUC(0-8), terminal half-life, and total body clearance were 7.06 microg/ml, 3.62 microg/ml, 37.4 microg x h/ml, 7.2 h, and 9.4 liters/h (0.12 liters/h/kg), respectively. Pharmacokinetic profiles of levofloxacin in HIV-infected patients did not appear to be affected by the concomitant administration of AZT; nor were AZT pharmacokinetics altered by levofloxacin. Oral administration of 350 mg of levofloxacin hemihydrate every 8 h appeared to be well tolerated by the subjects. There were no apparent differences in adverse events between the two treatment groups. There were no clinically significant changes from baseline in any laboratory parameter or vital sign following treatments observed in this study. The study results suggest that there is no need for levofloxacin dosage adjustment in HIV-seropositive subjects who concomitantly receive AZT.

scholarly journals Spin-up in a tank induced by a rotating bluff body

1999 ◽  
Vol 388 ◽  
pp. 49-68 ◽  
Author(s):  
D. MAYNES ◽  
J. KLEWICKI ◽  
P. McMURTRY
Keyword(s):  
Steady State ◽  
Turbulent Diffusion ◽  
Bluff Body ◽  
Fluid Velocity ◽  
Tangential Velocity ◽  
The Body ◽  
Mean Flow ◽  
Velocity Fluctuations ◽  
Acceleration Rate ◽  
Time Required

Spin-up of a turbulent flow in a cylindrical tank caused by a rotating bluff body has been investigated using flow visualization, fluid velocity measurements, and hydrodynamic torque measurements. During the spin-up process three distinct temporal regimes exist. These regimes are: (i) a build-up regime where the torque and the tangential velocity fluctuations in the close proximity of the body remain constant; (ii) a decay regime where these quantities decay with power-law relations; and (iii) a mean flow steady state where these values remain relatively constant. Experiments were conducted in two tanks differing in volume by a factor of 80 and with a large range of bluff body sizes. A non-dimensional time scale, τ, based upon turbulent diffusion is determined and the tangential velocity fluctuations and torque coefficient start to decay at a fixed value of τ. Likewise, steady state is attained at a larger fixed value of τ. This time scaling is physically based upon the time required for momentum to be transferred over the entire tank volume due to turbulent diffusion, and is general for any body size, tank size, rotation rate, and acceleration rate.

scholarly journals Computer simulations of propofol infusions for total intravenous anaesthesia in dogs : review article

2009 ◽  
Vol 80 (1) ◽  
Author(s):  
K.E. Joubert
Keyword(s):  
Steady State ◽  
Plasma Concentration ◽  
Simulated Data ◽  
The Body ◽  
Published Data ◽  
Total Intravenous Anaesthesia ◽  
International Treaties ◽  
Duration Of Action ◽  
Intravenous Anaesthesia ◽  
Anaesthetic Depth

The volatile anaesthetic agents halothane, isoflurane and enflurane are all chlorofluorocarbons and according to international treaties, their emission into the atmosphere will be prohibited from the year 2030. The agents desflurane and sevoflurane are fluorinated hydrocarbons and act as greenhouse gases. The future of veterinary anaesthesia could be dependent on the development of total intravenous anaesthesia. Drugs utilised in total intravenous anaesthesia (TIVA) should have a short duration of action and no tendency to accumulate in the body. Propofol has been the dominant agent used. Computer technology has enabled targeted plasma concentration controlled infusions to replace manual infusion regimens. This study simulated the pharmacokinetics of various infusion regimens similar to those used in clinical practice using previously published pharmocokinetic data. Bolus doses of 0, 4, 6 and 8 mg/kg were simulated in combination with infusion rates of 0, 0.2, 0.3 and 0.4 mg/kg/min for either 240 or 1440 min. The computer was also programmed to maintain a steady state plasma concentration based on the previous simulated data. Generated data were then compared with published data. Changes in the context-sensitive half-life for propofol were also evaluated. Results showed that the generated data were similar to published data. A decrease in plasma concentration to levels associated with a light plane of anaesthesia was evident even when the highest bolus dose and infusion rate were used. There was a slow rise in plasma concentration when only an infusion was used. A lightening of anaesthetic plane may be evident early in the course of TIVA and careful monitoring of anaesthetic depth is required. As the duration of the infusion increased, plasma concentration steadily rose but achieved 95 % of the steady state by 204 min. The most dramatic changes in plasma concentration occurred in the first hour of an infusion. Similarly, the infusion rates decreased most in the first 70 min. Most changes in anaesthetic depth are likely to occur early in the course of TIVA and careful observation of anaesthetic depth is required.

Clinical Pharmacokinetics of Chlorpheniramine

1984 ◽  
Vol 18 (9) ◽  
pp. 701-707 ◽  
Author(s):  
Martha M. Rumore
Keyword(s):  
Half Life ◽  
The Body ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Elimination Kinetics ◽  
Clinical Pharmacokinetics ◽  
Interindividual Variations ◽  
First Pass ◽  
Dose Levels ◽  
Kinetics Of

The clinical pharmacokinetics of chlorpheniramine are reviewed. Recent studies have established that the half-life of chlorpheniramine is longer than previously reported. Chlorpheniramine has a serum half-life of ∼20 hours in adults, and elimination from the body is primarily by metabolism to monodesmethyl and didesmethyl compounds. The half-life is increased in the presence of renal dysfunction and decreased in children. The exact mechanism of the presystemic first-pass elimination and the effects of dose levels on the process presently are unclear. Biopharmaceutical and pharmacokinetic studies after single or multiple doses in humans reveal wide interindividual variations in pharmacokinetics. Age, dialysis, urinary pH and flow influence the elimination kinetics of chlorpheniramine. Attention is brought to major issues that need further clarification to optimize drug therapy with this antihistamine. The use of pharmacokinetic parameters of chlorpheniramine for clinical application is discussed.

scholarly journals Starvation Ketosis and the Kidney

2021 ◽  
Vol 52 (6) ◽  
pp. 467-478
Author(s):  
Biff F. Palmer ◽  
Deborah J. Clegg
Keyword(s):  
Ketone Bodies ◽  
Waste Product ◽  
Sglt2 Inhibitor ◽  
Glucose Production ◽  
The Body ◽  
Urine Ph ◽  
Salicylate Intoxication ◽  
Alcoholic Ketoacidosis ◽  
Clinical Conditions

<b><i>Background:</i></b> The remarkable ability of the body to adapt to long-term starvation has been critical for survival of primitive man. An appreciation of these processes can provide the clinician better insight into many clinical conditions characterized by ketoacidosis. <b><i>Summary:</i></b> The body adapts to long-term fasting by conserving nitrogen, as the brain increasingly utilizes keto acids, sparing the need for glucose. This shift in fuel utilization decreases the need for mobilization of amino acids from the muscle for purposes of gluconeogenesis. Loss of urinary nitrogen is initially in the form of urea when hepatic gluconeogenesis is dominant and later as ammonia reflecting increased glutamine uptake by the kidney. The carbon skeleton of glutamine is utilized for glucose production and regeneration of consumed HCO<sub>3</sub><sup>−</sup>. The replacement of urea with NH<sub>4</sub><sup>+</sup> provides the osmoles needed for urine flow and waste product excretion. Over time, the urinary loss of nitrogen is minimized as kidney uptake of filtered ketone bodies becomes more complete. Adjustments in urine Na<sup>+</sup> serve to minimize kidney K<sup>+</sup> wasting and, along with changes in urine pH, minimize the likelihood of uric acid precipitation. There is a sexual dimorphism in response to starvation. <b><i>Key Message:</i></b> Ketoacidosis is a major feature of common clinical conditions to include diabetic ketoacidosis, alcoholic ketoacidosis, salicylate intoxication, SGLT2 inhibitor therapy, and calorie sufficient but carbohydrate-restricted diets. Familiarity with the pathophysiology and metabolic consequences of ketogenesis is critical, given the potential for the clinician to encounter one of these conditions.

scholarly journals Preparation and Pharmacokinetic Study of Daidzein Long-Circulating Liposomes

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Qiao Wang ◽  
Wenjin Liu ◽  
Junjun Wang ◽  
Hong Liu ◽  
Yong Chen
Keyword(s):  
Single Dose ◽  
Drug Concentration ◽  
Drug Loading ◽  
Plasma Drug Concentration ◽  
The Body ◽  
Molar Ratio ◽  
Terminal Phase ◽  
Plasma Drug ◽  
Ultrasonic Time ◽  
Time Required

Abstract In this study, daidzein long-circulating liposomes (DLCL) were prepared using the ultrasonication and lipid film-hydration method. The optimized preparation conditions by the orthogonal design was as follows: 55 to 40 for the molar ratio of soybean phosphatidylcholine (SPC) to cholesterol, 1 to 10 for the mass ratio of daidzein to total lipid (SPC and cholesterol) (w:w), the indicated concentration of 5% DSPE-mPEG2000 (w:w), 50 °C for the hydration temperature, and 24 min for the ultrasonic time. Under these conditions, the encapsulation efficiency and drug loading of DLCL were 85.3 ± 3.6% and 8.2 ± 1.4%, respectively. The complete release times of DLCL in the medium of pH 1.2 and pH 6.9 increased by four- and twofold of that of free drugs, respectively. After rats were orally administered, a single dose of daidzein (30 mg/kg) and DLCL (containing equal dose of daidzein), respectively, and the MRT0−t (mean residence time, which is the time required for the elimination of 63.2% of drug in the body), t1/2 (the elimination half-life, which is the time required to halve the plasma drug concentration of the terminal phase), and AUC0−t (the area under the plasma drug concentration-time curve, which represents the total absorption after a single dose and reflects the drug absorption degree) of daidzein in DLCL group, increased by 1.6-, 1.8- and 2.5-fold as compared with those in the free group daidzein. Our results indicated that DLCL could not only reduce the first-pass effect of daidzein to promote its oral absorption, but also prolong its mean resident time to achieve the slow-release effect.

scholarly journals A Feasibility Study of Kinematic Characteristics on the Upper Body According to the Shooting of Elite Disabled Archery Athletes

2021 ◽  
Vol 18 (6) ◽  
pp. 2962
Author(s):  
Tae-Whan Kim ◽  
Jae-Won Lee ◽  
Seoung-Ki Kang ◽  
Kyu-Yeon Chae ◽  
Sang-Hyup Choi ◽  
...  
Keyword(s):  
The Body ◽  
Lower Limbs ◽  
Upper Body ◽  
Movement Trajectory ◽  
Phase 2 ◽  
Kinematic Characteristics ◽  
Significant Difference ◽  
Athletes With Disabilities ◽  
Body Center ◽  
Time Required

The purpose of this study is to compare and analyze the kinematic characteristics of the upper limb segments during the archery shooting of Paralympic Wheelchair Class archers (ARW2—second wheelchair class—paraplegia or comparable disability) and Paralympic Standing Class archers (ARST—standing archery class—loss of 25 points in the upper limbs or lower limbs), where archers are classified according to their disability grade among elite disabled archers. The participants of this study were selected as seven elite athletes with disabilities by the ARW2 (n = 4) and ARST (n = 3). The analysis variables were (1) the time required for each phase, (2) the angle of inclination of the body center, (3) the change of trajectory of body center, and (4) the change of the movement trajectory of the bow center by phase when performing six shots in total. The ARW2 group (drawing phase; M = 2.228 s, p < 0.05, holding phase; M = 4.414 s, p < 0.05) showed a longer time than the ARST group (drawing phase; M = 0.985 s, holding phase; M = 3.042 s), and the angle of the body did not show a significant difference between the two groups. Additionally, in the direction of the anteroposterior axis in the drawing phase, the change in the movement trajectory of the body center showed a more significant amount of change in the ARW2 group than in the ARST group, and the change in the movement trajectory of the bow center did not show a significant difference between the two groups.

scholarly journals Metabolism of inorganic sulphate in the isolated perfused rat liver. Effect of sulphate concentration on the rate of sulphation by phenol sulphotransferase

1978 ◽  
Vol 176 (3) ◽  
pp. 959-965 ◽  
Author(s):  
Gerard J. Mulder ◽  
Katja Keulemans
Keyword(s):  
Steady State ◽  
Plasma Concentration ◽  
Rat Liver ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Perfusion Medium ◽  
Physiological Concentration ◽  
Sulphate Concentration ◽  
Inorganic Sulphate

1. The metabolism of inorganic [35S]sulphate (Na235SO4) was studied in the isolated perfused rat liver at three initial concentrations of inorganic sulphate in the perfusion medium (0, 0.65 and 1.30mm), in relation to sulphation and glucuronidation of a phenolic drug, harmol (7-hydroxy-1-methyl-9H-pyrido[3,4-b]indole). 2. [35S]Sulphate rapidly equilibrated with endogenous sulphate in the liver. It was excreted in bile and reached, at the lowest concentration in the perfusion medium, concentrations in bile that were much higher than those in the perfusion medium; at the higher sulphate concentrations, these concentrations were equal. The physiological concentration of inorganic sulphate in the liver, available for sulphation of drugs, is similar to the plasma concentration. 3. At zero initial inorganic sulphate in the perfusion medium, the rate of sulphation was very low and harmol was mainly glucuronidated. At 0.65mm-sulphate glucuronidation was much decreased and considerable sulphation took place, indicating efficient competition of conjugation by sulphation. At 1.30mm-sulphate the sulphation increased still further. 4. The results suggest that an important factor in sulphation is the relatively high Km of synthesis of adenosine 3′-phosphate 5′-sulphatophosphate (the co-substrate of sulphation) for inorganic sulphate, which is of the order of the plasma concentration of inorganic sulphate. The steady-state adenosine 3′-phosphate 5′-sulphatophosphate concentration may determine the rate of sulphate conjugation of drugs in the rat in vivo.

On the Regulation of the Respiration in Reptiles

1961 ◽  
Vol 38 (2) ◽  
pp. 301-314 ◽  
Author(s):  
BODIL NIELSEN
Keyword(s):  
Steady State ◽  
Body Temperature ◽  
Metabolic Rate ◽  
Temperature Interval ◽  
Normal Values ◽  
Pulmonary Ventilation ◽  
The Body ◽  
Respiratory Frequency ◽  
Temperature Changes ◽  
Instantaneous Increase

1. In two species of Lacerta (L. viridis and L. sicula) the effects on respiration of body temperature (changes in metabolic rate) and of CO2 added to the inspired air were studied. 2. Pulmonary ventilation increases when body temperature increases. The increase is brought about by an increase in respiratory frequency. No relationship is found between respiratory depth and temperature. 3. The rise in ventilation is provoked by the needs of metabolism and is not established for temperature regulating purposes (in the temperature interval 10°-35°C). 4. The ventilation per litre O2 consumed has a high numerical value (about 75, compared to about 20 in man). It varies with the body temperature and demonstrates that the inspired air is better utilized at the higher temperatures. 5. Pulmonary ventilation increases with increasing CO2 percentages in the inspired air between o and 3%. At further increases in the CO2 percentage (3-13.5%) it decreases again. 6. At each CO2 percentage the pulmonary ventilation reaches a steady state after some time (10-60 min.) and is then unchanged over prolonged periods (1 hr.). 7. The respiratory frequency in the steady state decreases with increasing CO2 percentages. The respiratory depth in the steady state increases with increasing CO2 percentages. This effect of CO2 breathing is not influenced by a change in body temperature from 20° to 30°C. 8. Respiration is periodically inhibited by CO2 percentages above 4%. This inhibition, causing a Cheyne-Stokes-like respiration, ceases after a certain time, proportional to the CO2 percentage (1 hr. at 8-13% CO2), and respiration becomes regular (steady state). Shift to room air breathing causes an instantaneous increase in frequency to well above the normal value followed by a gradual decrease to normal values. 9. The nature of the CO2 effect on respiratory frequency and respiratory depth is discussed, considering both chemoreceptor and humoral mechanisms.

Treatment of hyperthyroidism with a small single daily dose of methimazole

1988 ◽  
Vol 119 (1) ◽  
pp. 139-144 ◽  
Author(s):  
Yasuo Mashio ◽  
Mutsuo Beniko ◽  
Akemi Ikota ◽  
Hiroaki Mizumoto ◽  
Haruhiko Kunita
Keyword(s):  
Divided Dose ◽  
Dose Regimen ◽  
Single Daily Dose ◽  
Once Daily ◽  
Daily Dose ◽  
The Mean ◽  
Time Required ◽  
Daily Dose Regimen ◽  
Mean Time ◽  
Immunoglobulin Levels

Abstract. A prospective randomized trial with the conventional divided doses (10 mg 3 times daily, N = 29) and a small single daily dose (15 mg once daily, N = 25) of methimazole for the treatment of Graves' hyperthyroidism was performed. Within 8 weeks, almost 80% of the patients in both groups became euthyroid. The mean time required to achieve the euthyroid state was 6.0 ± 2.8 and 6.0 ± 3.8 weeks, respectively. TSH binding inhibitor immunoglobulin was found in about 90% of the patients in both groups before methimazole treatment. However, a gradual fall of its levels was observed in nearly all patients after treatment. There was no difference in the mean levels of TSH binding inhibitor immunoglobulin between the two groups during therapy. We conclude that the single daily dose regimen of 15 mg of methimazole will control Graves' hyperthyroidism in most patients, and TSH binding inhibitor immunoglobulin levels decrease in this regimen in the same way as with the conventional divided dose regimen (10 mg 3 times daily).

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