Influence or age and sex on the kinetics of intravenously administered L-phenylalanine.

1982 ◽  
Vol 28 (1) ◽  
pp. 204-206 ◽  
Author(s):  
R Jagenburg ◽  
C G Regårdh ◽  
S Rödjer
Keyword(s):  
Total Body Clearance ◽  
Kinetic Studies ◽  
Compartment Model ◽  
Peripheral Compartment ◽  
Two Compartment Model ◽  
Total Body ◽  
Kinetics Of ◽  
Effect Of Age ◽  
Age And Sex ◽  
Body Clearance

Abstract We studied the kinetics of intravenously administered L-phenylalanine with respect to the effect of age and sex, using a two-compartment model. We found that the volume of the peripheral compartment and total body clearance decrease with age. The sex-related influence was less obvious when distribution volumes and total body clearance were corrected for differences in body size. We emphasize the necessity of having age-matched control subjects in kinetic studies.

A toxicokinetic analysis in a patient with acute glufosinate poisoning

1999 ◽  
Vol 18 (5) ◽  
pp. 305-308 ◽  
Author(s):  
Y Hirose ◽  
M Kobayashi ◽  
K Koyama ◽  
Y Kohda ◽  
T Tanaka ◽  
...  
Keyword(s):  
Total Body Clearance ◽  
Artificial Ventilation ◽  
Compartment Model ◽  
Toxic Dose ◽  
Glufosinate Ammonium ◽  
Two Compartment Model ◽  
Serial Change ◽  
Total Body ◽  
Apparent Distribution ◽  
Body Clearance

Incidents of poisoning in humans caused by the ingestion of the glufosinate ammonium containing herbicides are gradually increasing in Japan. This poisoning is characterized by various neurological symptoms such as disturbances of consciousness, convulsions and apnea which appear after an asymptomatic interval of several hours. We studied the toxicokinetics of glufosinate in a patient with this poisoning successfully treated without extracorporeal hemopurification. A 65-year-old male ingested BASTA, which contains 20% w/v of glufosinate ammonium, about 300 ml, more than the estimated human toxic dose. Four and a half hours after ingestion, he showed speech ataxia and systemic tremor. He was prophylactically intubated before the occurrence of serious respiratory failure. After 5 days of artificial ventilation he was extubated and discharged without any sequelae. We studied the serial change of serum glufosinate concentration every 3-6 h and assessed the urinary excretion of glufosinate every 24 h. The absorbed amount of glufosinate was estimated from the cumulative excreted in urine. Toxicokinetic analysis was performed using the two-compartment model. The changes in serum glufosinate concentration exhibited T1/2α of 1.84 and T1/2α of 9.59 h. The apparent distribution volume at b-phase and the total body clearance were 1.44 l/kg and 86.6 ml/min, respectively. Renal clearance was estimated to be 77.9 ml/ min. The indication for extracorporeal hemopurification for this poisoning has been discussed.

Detection of heterozygotes for phenylketonuria. Total body phenylalanine clearance and concentrations of phenylalanine and tyrosine in the plasms of fasting subjects compared.

1977 ◽  
Vol 23 (9) ◽  
pp. 1654-1660 ◽  
Author(s):  
R Jagenburg ◽  
C G Regårdh ◽  
S Rödjer
Keyword(s):  
Total Body Clearance ◽  
Compartment Model ◽  
Central Compartment ◽  
Kinetic Evaluation ◽  
Plasma Phenylalanine ◽  
Two Compartment Model ◽  
Total Body ◽  
Elimination Curve ◽  
Body Clearance

Abstract Two tests have been compared for detection of heterozygotes for phenylketonuria, one based on determination of plasma phenylalanine and tyrosine concentrations in fasting individuals and the other on kinetic evaluation of the plasma elimination curve after intravenous loading with L-phenylalanine. The plasma elimination curve was biexponential and the kinetics were evaluated according to the two-compartment model. The constant, beta, expressing the rate of elimination from plasma at pseudo-equilibrium, the rate constant for the elimination from the central compartment, and the total body clearance were determined. Of these three, total body clearance, which on the average was reduced by 32% in the phenylketonuric heterozygotes, showed the best discriminatory ability, but was not better than the information on concentrations of phenylalanine and tyrosine in detecting heterozygotes for phenylketonuria.

Disposition Kinetics of lincomycin following intravenous administration in hypothyroid goats

2019 ◽  
Author(s):  
Meemansha Sharma ◽  
Vinod Kumar Dumka ◽  
Saloni Singla ◽  
Rajdeep Kaur ◽  
Raushan Kumar Singh
Keyword(s):  
Dose Rate ◽  
Intravenous Administration ◽  
Half Life ◽  
Total Body Clearance ◽  
Small Ruminants ◽  
Blood Samples ◽  
Elimination Half ◽  
Total Body ◽  
Kinetics Of ◽  
Body Clearance

Hypothyroidism is a common disorder of small ruminants and is expected to alter the pharmacokinetics of drugs. Hypothyroidism was induced by feeding thiourea at the dose rate 50 mg.kg-1 daily for 28 days to goats. Disposition of lincomycin, after intravenous administration at dose rate 10 mg/kg, was investigated in hypothyroid goats to determine the potential dosage regimen against susceptible microorganisms. Blood samples were collected from 1 min to 24 h of drug administration. The drug was detected in plasma up to 8 h and lincomycin was rapidly distributed from blood to the tissue, as evidenced by the high value of the distribution coefficient (mean ± SEM) 12.3±1.09 h-1. The large Vd (1.78±0.18 L/kg) indicated vast tissue distribution of lincomycin in goats. The elimination half life, AUC and total body clearance were 3.99± 0.25 h, 33.2±1.71 ìg.h/mL and 0.31±0.02 L/h/kg, respectively. Based on results, lincomycin in hypothyroid goats is suggested to be repeated at 12 h interval for organisms sensitive to lincomycin having MIC up to 0.1 µg.ml-1.

Asymptomatic Theophylline Overdose

1980 ◽  
Vol 14 (11) ◽  
pp. 783-785 ◽  
Author(s):  
Wayne Snodgrass ◽  
Dennis Sawyer ◽  
Christopher S. Conner ◽  
Barry H. Rumack ◽  
Robert G. Peterson ◽  
...  
Keyword(s):  
Cardiac Arrhythmias ◽  
Total Body Clearance ◽  
Clinical Signs ◽  
Serum Levels ◽  
High Serum ◽  
Theophylline Overdose ◽  
Saturation Kinetics ◽  
Total Body ◽  
Kinetics Of ◽  
Body Clearance

A case of severe theophylline overdose is described in which clinical signs of toxicity initially were minimal despite extremely high serum drug levels. Hemodialysis was performed because of the risk of seizures and cardiac arrhythmias. The predialysis, dialysis, and postdialysis half-lives were 13.1, 4.3, and 6.7 hours, respectively. Corresponding total body clearance values were 23.8, 72.5, and 46.3 ml/kg/h. The patient showed apparent saturation kinetics of theophylline clearance at high serum levels. Hemodialysis is effective for enhancing the removal of theophylline.

Effect of a Moderate Blood Exchange with Fluosol-Da 20% on the Disposition of Digoxin in the Dog

1987 ◽  
Vol 110 ◽  
Author(s):  
John F. Hoke ◽  
William R. Ravis
Keyword(s):  
Sham Group ◽  
Total Body Clearance ◽  
Blood Substitute ◽  
Volume Of Distribution ◽  
Intravenous Dose ◽  
Blood Exchange ◽  
Group A ◽  
Total Body ◽  
Kinetics Of ◽  
Body Clearance

AbstractThe effect of a perfluorochemical blood substitute (Fluosol-DA 20%) on the disposition kinetics of digoxin in the dog was studied. An intravenous dose of digoxin was administered at either 0.25 or 24 hours following a 30% blood exchange with the dog's own blood (SHAM group) or Fluosol-DA (treatment group). A significant change in the initial volume of distribution and mean residence time in the serum was noted when digoxin was administered 0.25 hours after the Fluosol-DA blood exchange. This volume of distribution change was not observed when digoxin was administered 24 hours after the Fluosol-DA blood exchange. No change in the t1/2, total body clearance, or volume of distribution at steady-state was observed in any of the treatments. No change in the partitioning of digoxin in the blood was noted following Fluosol-DA administration.

scholarly journals A comparison of the short-term kinetics of zinc metabolism in women during fasting and following a breakfast meal

1998 ◽  
Vol 80 (4) ◽  
pp. 363-370 ◽  
Author(s):  
Nicola M. Lowe ◽  
Leslie R. Woodhouse ◽  
Janet C. King
Keyword(s):  
Energy Content ◽  
Compartment Model ◽  
Zinc Metabolism ◽  
Short Term ◽  
Compartment System ◽  
Breakfast Meal ◽  
Physiological Importance ◽  
Two Compartment Model ◽  
Zn Concentration ◽  
Kinetics Of

The physiological importance and mechanism of the postprandial fall in plasma Zn concentration is not well understood. In order to gain further information on this apparent redistribution of plasma Zn, a stable isotope, 70Zn, was used to study the effect of a breakfast meal on plasma Zn kinetics. Nine women participated in two trials, a fasting trial and a breakfast-meal trial; five of the women participated in a third trial in which the energy content of the breakfast meal was doubled. At each trial, 0.1mg of 70Zn was infused intravenously, and the plasma disappearance of the isotope was analysed using a two-compartment model of Zn kinetics. Plasma Zn concentration fell significantly following the two trials in which the subjects were given meals, reaching low points that were 13 and 19 %, respectively, below concentrations at comparable times during the fasting trial. Kinetic analysis revealed that after the doubled breakfast meal there was a significant fall (P < 0.007) in the size of the most rapidly turning over Zn pool (pool (a)) from 2.90 (se 0.13)mg in the fasting state to 2.47 (se 0.14) mg postprandially. The fractional turnover rate of pool (a) to other extravascular Zn pools, i.e. outside the two-compartment system, was also significantly elevated after the doubled breakfast meal (P < 0.05). These results suggest that the decline in plasma Zn concentration following a meal is due to a redistribution of Zn from the plasma to other more slowly turning over extravascular pools that may be involved in the assimilation and metabolism of fuels following food intake.

scholarly journals Pharmacokinetics of Intravenous Piperacillin Administration in Patients Undergoing On-Line Hemodiafiltration

2009 ◽  
Vol 53 (8) ◽  
pp. 3266-3268 ◽  
Author(s):  
Kook-Hwan Oh ◽  
Chiweon Kim ◽  
Hankyu Lee ◽  
Hajeong Lee ◽  
Ji Yong Jung ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Total Body Clearance ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Recovery Method ◽  
Elimination Half ◽  
On Line ◽  
The Mean ◽  
Total Body ◽  
Body Clearance

ABSTRACT The pharmacokinetic characteristics of piperacillin sodium were studied in five volunteers undergoing on-line hemodiafiltration (HDF). The subjects were given 2 g of piperacillin sodium intravenously over 1 min and placed on on-line HDF for 4 h starting at 60 min after the piperacillin infusion. Noncompartmental models were employed for estimation of the pharmacokinetic parameters, and intradialytic piperacillin clearance was calculated by the recovery method. The mean volume of distribution and the elimination half-life were 0.27 ± 0.13 liter/kg (mean ± standard deviation) and 1.1 ± 0.6 h, respectively. The total body clearance of piperacillin was 0.19 ± 0.08 liter/h/kg. Piperacillin clearance through on-line HDF was 0.11 ± 0.06 liter/h/kg. The mean serum piperacillin concentration was 4.0 ± 1.9 μg/ml at the end of the 4-h on-line HDF session. The concentration of infused piperacillin recovered in the dialysate was 527 ± 236 mg (26.3% ± 11.8%). We suggest the replacement of 500 mg of piperacillin after each on-line HDF session.

Population pharmacokinetic modeling and dosing simulations of tobramycin in pediatric patients with cystic fibrosis

2021 ◽  
Author(s):  
Antonin Praet ◽  
Laurent Bourguignon ◽  
Florence Vetele ◽  
Valentine Breant ◽  
Charlotte Genestet ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Dose Adjustment ◽  
Total Body Weight ◽  
Compartment Model ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Time Curve ◽  
Population Pharmacokinetic Modeling ◽  
Two Compartment Model ◽  
Total Body

Initial dosing and dose adjustment of intravenous tobramycin in cystic fibrosis children is challenging. The objectives of this study were to develop nonparametric population pharmacokinetic (PK) models of tobramycin in children with CF to be used for dosage design and model-guided therapeutic drug monitoring. We performed a retrospective analysis of tobramycin PK data in our CF children center. The Pmetrics package was used for nonparametric population PK analysis and dosing simulations. Both the maximal concentration over the MIC (Cmax/MIC) and daily area under the concentration-time curve to the MIC (AUC 24 /MIC) ratios were considered as efficacy target. Trough concentration (Cmin) was considered as the safety target. A total of 2884 tobramycin concentrations collected in 195 patients over 9 years were analyzed. A two-compartment model including total body weight, body surface area and creatinine clearance as covariates best described the data. A simpler model was also derived for implementation into the BestDose software to perform Bayesian dose adjustment. Both models were externally validated. PK/PD simulations with the final model suggest that an initial dose of tobramycin of 15 to 17.5 mg/kg/day was necessary to achieve Cmax/MIC ≥ 10 values for MIC values up to 2 mg/L in most patients. The AUC 24 /MIC target was associated with larger dosage requirements and higher Cmin. A daily dose of 12.5 mg/kg would optimize both efficacy and safety target attainment. We recommend to perform tobramycin TDM, model-based dose adjustment, and MIC determination to individualize intravenous tobramycin therapy in children with CF.

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