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Antimicrobial Agents and Chemotherapy Apr 2013The pharmacokinetics of intravenous anidulafungin in adult intensive care unit (ICU) patients were assessed in this study and compared with historical data from a... (Randomized Controlled Trial)
Randomized Controlled Trial
The pharmacokinetics of intravenous anidulafungin in adult intensive care unit (ICU) patients were assessed in this study and compared with historical data from a general patient population and healthy subjects. Intensive plasma sampling was performed over a dosing interval at steady state from 21 ICU patients with candidemia/invasive candidiasis. All patients received the recommended dosing regimen (a 200-mg loading dose on day 1, followed by a daily 100-mg maintenance dose), except for a 54-year-old 240-kg female patient (who received a daily 150-mg maintenance dose instead). Plasma samples were assayed for anidulafungin using a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters in ICU patients were calculated by a noncompartmental method. With the exclusion of the 240-kg patient, the median (minimum, maximum) age, weight, and body mass index (BMI) of 20 ICU patients were 57 (39, 78) years, 65 (48, 106) kg, and 23.3 (16.2, 33.8) kg/m(2), respectively. The average anidulafungin area under the curve over the 24-hour dosing interval (AUC(0-24)), maximum concentration (C(max)), and clearance (CL) in 20 ICU patients were 92.7 mg · h/liter, 7.7 mg/liter, and 1.3 liters/h, respectively. The exposure in the 240-kg patient at a daily 150-mg dose was within the range observed in ICU patients overall. The average AUC(0-24) and Cmax in the general patient population and healthy subjects were 110.3 and 105.9 mg · h/liter and 7.2 and 7.0 mg/liter, respectively. The pharmacokinetics of anidulafungin in ICU patients appeared to be comparable to those in the general patient population and healthy subjects at the same dosing regimen.
Topics: Adult; Aged; Anidulafungin; Antifungal Agents; Candidemia; Candidiasis, Invasive; Critical Illness; Echinocandins; Female; Humans; Male; Middle Aged
PubMed: 23335738
DOI: 10.1128/AAC.02139-12 -
Medecine Sciences : M/S Apr 2021The kidney plays a major role to maintain the constancy of the "milieu intérieur" by adjusting the urinary excretion of water and solutes to the requirement of the body... (Review)
Review
The kidney plays a major role to maintain the constancy of the "milieu intérieur" by adjusting the urinary excretion of water and solutes to the requirement of the body balance. This function is coordinated with elimination of waste products generated among others by the catabolism of proteins and nucleic acids. To cope with these two major functions, the human kidneys generate each day about 180 L of ultrafiltrate from plasma and reabsorbs the vast majority of filtered water and solutes to excrete daily about one-two liter(s) of urine containing concentrations of sodium, potassium and chloride ranging from 20 to 200 mM. The final adjustment of urine composition is finely tuned along the aldosterone-sensitive distal nephron (ASDN) which includes the distal convoluted tubule and the collecting system (connecting tubule and collecting duct). Sodium reabsorption is predominant along the distal tubule if potassium must be spared, or along the collecting system when large amounts of potassium must be secreted. Nephrotic syndrome is characterized by heavy proteinuria consecutive to a glomerular injury, associated with renal sodium and water retention taking initially place along ASDN and leading to edema.
Topics: Animals; Body Water; Chlorides; Humans; Kidney Tubules, Collecting; Kidney Tubules, Distal; Kidney Tubules, Proximal; Loop of Henle; Mice; Nephrons; Nephrotic Syndrome; Nucleic Acids; Potassium; Proteins; Renin-Angiotensin System; Sodium; Urine
PubMed: 33908853
DOI: 10.1051/medsci/2021032 -
Australian and New Zealand Journal of... Jun 2012
Topics: Beverages; Drinking; Energy Metabolism; Environment; Humans; Nutritional Requirements
PubMed: 22672023
DOI: 10.1111/j.1753-6405.2012.00866.x -
Antimicrobial Agents and Chemotherapy Sep 1996Single-dose and steady-state pharmacokinetics of antivirally acting hypericin (H) and pseudohypericin (PH) were studied in 13 healthy volunteers by administration of St.... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Single-dose and steady-state pharmacokinetics of antivirally acting hypericin (H) and pseudohypericin (PH) were studied in 13 healthy volunteers by administration of St. John's Wort extract LI 160, a plantal antidepressant. Oral administration of 250, 750, and 1,500 micrograms of H and 526, 1,578, and 3,156 micrograms of PH resulted in median peak levels in plasma (Cmax) of 1.3, 7.2, and 16.6 micrograms/liter for H and 3.4, 12.1, and 29.7 micrograms/liter for PH, respectively. The Cmax and the area under the curve values for the lowest dose were disproportionally lower than those for the higher doses. A lag time of 1.9 h for H was remarkably longer than the 0.4-h lag time for PH. Median half-lives for absorption, distribution, and elimination were 0.6, 6.0, and 43.1 h after 750 micrograms of H and 1.3, 1.4, and 24.8 h after 1,578 micrograms of PH, respectively. Fourteen-day treatment with 250 micrograms of H and 526 micrograms of PH three times a day resulted in median steady-state trough levels of 7.9 micrograms/liter for H and 4.8 micrograms/liter for PH after 7 and 4 days, respectively; the corresponding Cssmax levels were 8.8 and 8.5 micrograms/liter, respectively. Kinetic parameters after intravenous administration of Hypericum extract (115 and 38 micrograms for H and PH, respectively) in two subjects corresponded to those estimated after an oral dosage. Both H and PH were initially distributed into a central volume of 4.2 and 5.0 liter, respectively. The mean distribution volumes at steady state were 19.7 liters for H and 39.3 liters for PH, and the mean total clearance rates were 9.2 ml/min for H and 43.3 ml/min for PH. The systemic availability of H and PH from LI 160 was roughly estimated to be 14 and 21%, respectively. Treatment with Hypericum extract, even in high doses, was well tolerated.
Topics: Administration, Oral; Adult; Anthracenes; Antiviral Agents; Area Under Curve; Body Weight; Chromatography, High Pressure Liquid; Double-Blind Method; Half-Life; Humans; Injections, Intravenous; Male; Perylene
PubMed: 8878586
DOI: 10.1128/AAC.40.9.2087 -
Journal of Nutritional Science 2021The study objective was to measure fluid intake and associations with background characteristics and hydration biomarkers in healthy, free-living, non-pregnant women...
The study objective was to measure fluid intake and associations with background characteristics and hydration biomarkers in healthy, free-living, non-pregnant women aged 15-69 years from Hargeisa city. We also wanted to estimate the proportion of euhydrated participants and corresponding biomarker cut-off values. Data from 136 women, collected through diaries and questionnaires, 24h urine samples and anthropometric measurements, were obtained with a cross-sectional, purposeful sampling from fifty-two school and health clusters, representing approximately 2250 women. The mean (95 % CI) 24 h total fluid intake (TFI) for all women was 2⋅04 (1⋅88, 2⋅20) litres. In multivariate regression with weight, age, parity and a chronic health problem, only weight remained a predictor ( 0.034, 0.0156 (l/kg)). Pure water, Somali tea and juice from powder and syrup represented 49⋅3, 24⋅6 and 11⋅7 % of TFI throughout the year, respectively. Mean (95 % CI) 24 h urine volume (Uvol) was 1⋅28 (1⋅17, 1⋅39) litres. TFI correlated strongly with 24 h urine units ( 0.67) and Uvol ( 0.59). Approximately 40 % of the women showed inadequate hydration, using a threshold of urine specific gravity (Usg) of 1⋅013 and urine colour (Ucol) of 4. Five percent had Usg > 1⋅020 and concomitant Ucol > 6, indicating dehydration. TFI lower cut-offs for euhydrated, non-breast-feeding women were 1⋅77 litres and for breast-feeding, 2⋅13 litres. Euhydration cut-off for Uvol was 0⋅95 litre, equalling 9⋅2 urine units. With the knowledge of adverse health effects of habitual hypohydration, Somaliland women should be encouraged to a higher fluid intake.
Topics: Adolescent; Adult; Aged; Biomarkers; Cross-Sectional Studies; Dehydration; Drinking; Female; Humans; Middle Aged; Osmolar Concentration; Somalia; Water-Electrolyte Balance; Young Adult
PubMed: 34527224
DOI: 10.1017/jns.2021.54 -
The Cochrane Database of Systematic... 2002Inhaled bronchodilators form the mainstay of treatment for acute exacerbations of COPD. Two types of agent are used routinely, either singly or in combination:... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Inhaled bronchodilators form the mainstay of treatment for acute exacerbations of COPD. Two types of agent are used routinely, either singly or in combination: anticholinergic agents and beta2-sympathomimetic agonists.
OBJECTIVES
To assess the effect of anti-cholinergic agents on lung function and dyspnea in patients with acute exacerbations of COPD, compared with placebo or short-acting beta-2 agonists.
SEARCH STRATEGY
A comprehensive search of the literature was carried out on MEDLINE, EMBASE, CINAHL and the Cochrane COPD Trials Register, using the terms: bronchodilator* OR ipratropium OR oxitropium. References listed in each included trial were searched for additional trial reports.
SELECTION CRITERIA
Studies were included if the participants were adult patients with a known diagnosis of COPD and had symptoms consistent with criteria for acute exacerbation of COPD. All randomized controlled trials that compared inhaled ipratropium bromide or oxitropium bromide to appropriate controls were considered. Appropriate control treatments included placebo, other bronchodilating agents, or combination therapies. Studies of acute asthma or ventilated patients were excluded.
DATA COLLECTION AND ANALYSIS
All trials that appeared to be relevant were assessed by two reviewers who independently selected trials for inclusion. Differences were resolved by consensus.
MAIN RESULTS
Four trials compared the short-term effects of ipratropium bromide vs. a beta2-agonist. Short-term changes in FEV1 (up to 90 minutes) showed no significant difference between beta2-agonist and ipratropium bromide treated patients. The differences were similar among the studies and when combined: Weighted Mean Difference (WMD) 0.0 liters (95% Confidence Interval (95% CI) -0.19, 0.19). There was no significant additional increase in change in FEV1 on adding ipratropium to beta2-agonist: WMD 0.02 liter (95% CI -0.08, 0.12). Long-term effects (24 hours) of the ipratropium bromide and beta2-agonist treatment combination were similar: WMD 0.05 liters (95%CI -0.14, 0.05). Neither of two studies found significant changes in PaO2, either short- or long-term, with ipratropium vs. beta-agonist, although one showed an increase in PaO2 in subjects receiving ipratropium bromide at 60 minutes. Adverse drug reactions included dry mouth and tremor.
REVIEWER'S CONCLUSIONS
There was no evidence that the degree of bronchodilation achieved with ipratropium bromide was greater than that using a short-acting beta2-agonist. The combination of a beta2-agonist and ipratropium did not appear to increase the effect on FEV1 more than either used alone.
Topics: Bronchodilator Agents; Cholinergic Antagonists; Humans; Ipratropium; Parasympatholytics; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Scopolamine Derivatives
PubMed: 12519615
DOI: 10.1002/14651858.CD003900 -
Asia Pacific Journal of Clinical... 2009Water is vital to food production: every calorie of plant food requires at least one litre of water, while one calorie of meat or dairy product can require up to 10... (Review)
Review
Water is vital to food production: every calorie of plant food requires at least one litre of water, while one calorie of meat or dairy product can require up to 10 litres of water. Water is supplied either through rainfall or through irrigation. Irrigated agriculture uses 18 per cent of agricultural land, and produces 40 per cent of agricultural products. But urbanisation, agricultural land degradation, the mandating of biofuels, drought and climate change are reducing the amount of water available to agriculture. The green revolution of last century doubled cereal production with only a very small increase in land. This century we need a blue revolution, a dramatic increase in the amount of food produced from irrigation or blue water. The blue revolution must be based on knowledge, with that knowledge accessible, and useful, to farmers in both the developed and developing world.
Topics: Agriculture; Animals; Australia; Climate Change; Environment; Food Supply; Green Chemistry Technology; Health Status; Humans; Water; Water Supply
PubMed: 19965339
DOI: No ID Found -
Antimicrobial Agents and Chemotherapy Jul 2017Ceftazidime-avibactam administered at 1.25 g every 8 h was used to treat multidrug-resistant bacteremia in a critically ill patient on continuous venovenous...
Ceftazidime-avibactam administered at 1.25 g every 8 h was used to treat multidrug-resistant bacteremia in a critically ill patient on continuous venovenous hemofiltration (CVVH). Prefiltration plasma drug concentrations of ceftazidime and avibactam were measured at 0, 1, 2, 4, 6, and 8 h along with postfiltration and ultrafiltrate concentrations at h 2 and h 6. Plasma pharmacokinetic parameters of ceftazidime and avibactam, respectively, were as follows: maximum plasma concentration (), 61.10 and 14.54 mg/liter; minimum plasma concentration (), 31.96 and 8.45 mg/liter; half-life (), 6.07 and 6.78 h; apparent volume of distribution at the steady state (), 27.23 and 30.81 liters; total clearance at the steady state (CL), 2.87 and 2.95 liters/h; area under the concentration-time curve from 0 to 8 h (AUC), 347.87 and 85.69 mg · h/liter. Concentrations of ceftazidime in plasma exceeded the ceftazidime-avibactam MIC (6 mg/liter) throughout the 8-h dosing interval. Mean CVVH extraction ratios for ceftazidime and avibactam were 14.44% and 11.53%, respectively, and mean sieving coefficients were 0.96 and 0.93, respectively. The calculated mean clearance of ceftazidime by CVVH was 1.64 liters/h and for avibactam was 1.59 liters/h, representing 57.1% of the total clearance of ceftazidime and 54.3% of the total clearance of avibactam. Further data that include multiple patients and dialysis modes are needed to verify the optimal ceftazidime-avibactam dosing strategy during critical illness and CVVH.
Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Ceftazidime; Critical Illness; Drug Combinations; Hemofiltration; Microbial Sensitivity Tests; Pseudomonas aeruginosa
PubMed: 28416553
DOI: 10.1128/AAC.00464-17 -
Antimicrobial Agents and Chemotherapy Jul 2015The tolerability, safety, and disposition of dihydroartemisinin (DHA) and piperaquine (PQ) were assessed in 32 pregnant (second/third trimester) and 33 nonpregnant Papua...
Population pharmacokinetics, tolerability, and safety of dihydroartemisinin-piperaquine and sulfadoxine-pyrimethamine-piperaquine in pregnant and nonpregnant Papua New Guinean women.
The tolerability, safety, and disposition of dihydroartemisinin (DHA) and piperaquine (PQ) were assessed in 32 pregnant (second/third trimester) and 33 nonpregnant Papua New Guinean women randomized to adult treatment courses of DHA-PQ (three daily doses) or sulfadoxine-pyrimethamine (SP)-PQ (three daily PQ doses, single dose of SP). All dose adminstrations were observed, and subjects fasted for 2 h postdose. Plasma PQ was assayed by using high-performance liquid chromatography, and DHA was assessed by using liquid chromatography-mass spectrometry. Compartmental pharmacokinetic models were developed using a population-based approach. Both regimens were well tolerated. There was an expected increase in the rate-corrected electrocardiographic QT interval which was independent of pregnancy and treatment. Two pregnant and two nonpregnant women had Plasmodium falciparum parasitemia which cleared within 48 h, and no other subject became slide positive for malaria during 42 days of follow-up. Of 30 pregnant women followed to delivery, 27 (90%) delivered healthy babies and 3 (10%) had stillbirths; these obstetric outcomes are consistent with those in the general population. The area under the plasma PQ concentration-time curve (AUC0-∞) was lower in the pregnant patients (median [interquartile range], 23,721 μg · h/liter [21,481 to 27,951 μg · h/liter] versus 35,644 μg · h/liter [29,546 to 39,541 μg · h/liter]; P < 0.001) in association with a greater clearance relative to bioavailability (73.5 liters/h [69.4 to 78.4] versus 53.8 liters/h [49.7 to 58.2]; P < 0.001), but pregnancy did not influence the pharmacokinetics of DHA. The apparent pharmacokinetic differences between the present study and results from other studies of women with uncomplicated malaria that showed no effect of pregnancy on the AUC0-∞ of PQ and greater bioavailability may reflect differences in postdose fat intake, proportions of women with malaria, and/or racial differences in drug disposition.
Topics: Adolescent; Adult; Antimalarials; Area Under Curve; Artemisinins; Biological Availability; Dietary Fats; Drug Combinations; Female; Follow-Up Studies; Food-Drug Interactions; Humans; Infant, Newborn; Malaria, Falciparum; Models, Statistical; Papua New Guinea; Pregnancy; Pregnancy Outcome; Pyrimethamine; Quinolines; Sulfadoxine; Young Adult
PubMed: 25963981
DOI: 10.1128/AAC.00326-15 -
Antimicrobial Agents and Chemotherapy Oct 2020Cycloserine is a WHO group B drug for the treatment of multidrug-resistant tuberculosis (TB). Pharmacokinetic/pharmacodynamic data for cycloserine when dosed as...
Cycloserine is a WHO group B drug for the treatment of multidrug-resistant tuberculosis (TB). Pharmacokinetic/pharmacodynamic data for cycloserine when dosed as terizidone are sparse. The aim of this analysis was to describe the population pharmacokinetics of cycloserine when administered as terizidone and predict the doses of terizidone attaining cycloserine exposures associated with efficacy. The plasma cycloserine level was measured 2 to 6 weeks after treatment initiation in patients hospitalized for second-line tuberculosis treatment. The pretreatment MICs of cycloserine were determined for the clinical isolates. We enrolled 132 participants with rifampicin-resistant TB; 79 were HIV positive. The median pretreatment MIC was 16 mg/liter. A one-compartment disposition model with two clearance pathways, nonrenal (0.35 liters/h) and renal (0.43 liters/h), described cycloserine pharmacokinetics well. Nonrenal clearance and the volume of distribution were allometrically scaled using fat-free mass. Smoking increased nonrenal clearance by 41%. Simulations showed that with daily doses of terizidone (750 mg and 1,000 mg for patients weighing ≤45 kg and >45 kg, respectively), the probability of maintaining the plasma cycloserine concentration above the MIC for more than 30% of the dosing interval (30% ) (which is associated with a 1.0-log-CFU/ml kill ) exceeded 90% at MIC values of ≤16 mg/liter, but the proportion of patients achieving 100% (which is associated with the prevention of resistance) was more than 90% only at MICs of ≤8 mg/liter. Based on a target derived , the WHO-recommended doses of terizidone are effective for cycloserine MICs of ≤8 mg/liter, and higher doses are required to prevent the development of resistance.
Topics: Cycloserine; Humans; Isoxazoles; Microbial Sensitivity Tests; Monte Carlo Method; Oxazolidinones; Tuberculosis, Multidrug-Resistant
PubMed: 32816738
DOI: 10.1128/AAC.01381-20