On the Origin of The Apparent Volume of Distribution and Its Significance in Solvent Extraction Methods

2021 ◽  
Vol 1 (1) ◽  
pp. 1-7
Author(s):  
Michalakis Savva
2012 ◽  
Vol 452-453 ◽  
pp. 1069-1073
Author(s):  
Yun Hua Hui ◽  
You Qiong Cai ◽  
Bing Feng ◽  
Wen Ruan ◽  
Hui Juan Yu

The pharmacokinetics of norfloxacin were investigated in the European eel after a single oral gavage of 10 mg norfloxacin per kg body weight. The concentrations of norfloxacin in the main tissues (kidney, muscle, hepatopancreas and blood) were simultaneously detected by HPLC. All of the concentration-time curves of norfloxacin in the plasma, muscle and liver were consistent with absorption of a two-compartment open kinetic model. Norfloxacin was widely distributed in different tissues in the European eel. Apparent volume of distribution (Vd) was 52.025 L/kg, 34.589 L/kg, 2.795 L/kg, and 0.969 L/kg, in plasma, muscle, liver and kidney, respectively. Norfloxacin in the eel was proved to eliminate slowly, and half-time (tβ1/2) in plasma, muscle, liver and kidney, was 201.222 h, 123.789 h, 120.634 h and 627473.495 h, respectively. Body clearance was 0.689 L / ( kg•h ), 1.793 L/( kg•h ), 0.097 L/( kg•h ) and 0.028 L /( kg•h ), in plasma, muscle, liver and kidney, respectively.


1979 ◽  
Vol 57 (8) ◽  
pp. 878-881 ◽  
Author(s):  
James E. Heavner ◽  
Duane C. Bloedow

Pharmacokinetic parameters of a ketamine (10 mg/kg, iv) bolus in decerebrate and intact cats were compared. A two-compartment open model best described the data in both groups. The apparent volume of distribution of the peripheral compartment, the apparent volume of distribution of the drug in the body, and the half-life of the postdistributive phase were significantly less (p < 0.05) in the decerebrate animals. These results emphasize the importance of correlating behavior and neuronal activity with plasma or blood concentrations of drug in animals rather than assuming that, for a given drug dose, blood (and thus tissue) levels of the agent will be similar regardless of how the animal is prepared for study.


PEDIATRICS ◽  
1981 ◽  
Vol 68 (4) ◽  
pp. 601-602
Author(s):  
M. Spino ◽  
J. J. Thiessen ◽  
A. Isles ◽  
H. Levison ◽  
S. M. MacLeod

We found the report by Feldman et al1 interesting with potential clinical application. However, we would like to point out an error in their determination of the apparent volume of distribution (V) and comment on both their methodology and results. They state that V was calculated by dividing the dose of the drug by the extrapolated y intercept for drug concentration at time 0. This method is correct for a drug which exhibits monoexponential elimination following a single intravenous dose.


Author(s):  
Hisham S. Abou-Auda ◽  
Eqbal Qaddour ◽  
Hussein Alsisi ◽  
Azizah Ajlan ◽  
Mohammad Alsebayel

Introduction: Tacrolimus is a macrolide immunosuppressant. It has a narrow therapeutic index and serious side effects which necessitate monitoring of tacrolimus blood concentration. The trough concentration of the drug may also differ based on the type of liver transplant. This study was conducted to investigate differences in pharmacokinetics between transplant types and to determine tacrolimus population pharmacokinetic in liver transplant recipients in Saudi Arabia. Method: Patients on tacrolimus, as the main immunosuppressant, who underwent liver transplant throughout2012-2014 were retrospectively studied. Demographic characteristic, tacrolimus blood trough concentrations, liver, renal, biochemistry, and hematology lab results were all collected. The pharmacokinetic parameters were estimated assuming one compartment model. Results: Tacrolimus pharmacokinetic parameters were found to be as following; elimination rate constant () 0.094 ±  0.0123, apparent volume of distribution () 112.48±63.033 L/hr, elimination half-life () 7.46± 1.01 hr and apparent total body clearance () 10.27± 5.69 L/hr (mean ± SD). Statistically significant difference was found between living-donor and deceased-donor liver transplant with respect to apparent clearance and apparent volume of distribution. Living-donor liver transplant recipients have apparent volume of distribution of 97.39±47.00 L (mean ± SD) and an apparent clearance of 8.89±4.24L/hr (mean± SD). On the other hand, deceased-donor liver transplant has an apparent clearance of 12.97±7.09L/hr (mean ± SD) and an apparent volume of distribution of 142.17± 78.65 L (mean ± SD). Conclusions: Tacrolimus pharmacokinetics parameters were accurately determined in liver transplant recipients in Saudi Arabia. The results of the present study can be clinically used in the therapeutic drug monitoring of tacrolimus in the individualization of drug dosage and taking the appropriate clinical decisions to prevent allograft rejection.


PEDIATRICS ◽  
1981 ◽  
Vol 68 (4) ◽  
pp. 602-603
Author(s):  
Charles H. Feldman ◽  
Vincent E. Hutchinson ◽  
Charles E. Pippenger ◽  
Thomas A. Blumenfeld ◽  
Bernard R. Feldman ◽  
...  

We appreciate the comments of Weinberger et al and Spino et al. The equation utilized in our original report to calculate the apparent volume of distribution (V) was in error, as it was based on determinations for drugs that exhibit monoexponential elimination following a single intravenous dose. The correct formula for oral dosing at steady state with a drug obeying one-compartment model kinetics is: V = F.X0/AUCτ. K, where F is the total fraction of dose reaching systemic circulation, X0, is the dose, AUCτ is the area under the curve during a dosing interval; K is the elimination rate constant.1


PEDIATRICS ◽  
1974 ◽  
Vol 54 (6) ◽  
pp. 713-717
Author(s):  
Gerhard Levy ◽  
Sumner J. Yaffe

The apparent volume of distribution (Vd) of salicylate was determined in 11 children, 4 months to 16 years old, who had ingested from about 36 to over 340 mg of salicylic acid (mainly as aspirin) per kilogram of body weight. Vd was calculated from the amount of salicylate in the body at a given time (as determined by the amount of total salicylates excreted in the urine and, where applicable, removed in peritoneal dialysis fluid after that time) and the concentration of salicylate in the plasma at the same time. This method of calculation is ideal for the nonlinearly eliminated salicylic acid and does not require any assumptions with respect to the nature of the pharmacokinetic model for salicylate distribution. The Vd for salicylate in the children ranged from 162 to 345 ml/kg and was larger at the higher doses. Plots of salicylate concentration in plasma versus amount of drug in the body were usually linear for a given patient, showing that Vd remained relatively constant over the time course of elimination of the drug in the patients studied. This indicates that a given plasma salicylate concentration in children who have ingested large doses reflects a larger amount of salicylate in the body than the same plasma concentration in children who ingested smaller doses of the drug. These observations help to rationalize and emphasize the usefulness of the Done nomogram (which involves estimation of the theoretical zero time plasma salicylate concentration by back extrapolation) for assessing the severity of salicylate intoxication.


1996 ◽  
Vol 271 (1) ◽  
pp. G156-G163 ◽  
Author(s):  
C. P. Hansen ◽  
F. Stadil ◽  
L. Yucun ◽  
J. F. Rehfeld

The elimination of carboxyamidated gastrin-17 and its glycine-extended precursor was studied in anesthetized pigs during constant-rate infusion. Extraction of amidated gastrin-17 was recorded in the hindlimb (42%), kidney (40%), head (32%, P < 0.001), and the gut (13%, P < 0.01). Elimination was not recorded in the liver, lungs, or heart. Extraction of glycine-extended gastrin-17 was measured in the kidney (36%), hindlimb (31%, P < 0.001), head (26%), and the gut (16%, P < 0.01), but not in the liver or the lungs. Glycine-extended gastrin-17 was not processed to amidated gastrin during infusion. The half-life, metabolic clearance rate, and apparent volume of distribution for amidated gastrin-17 were 3.5 +/- 0.4 min, 15.5 +/- 1.1 ml.kg-1.min-1, and 76.5 +/- 9.9 ml/kg, respectively, and for glycine-extended gastrin-17 were 4.3 +/- 0.6 min, 17.4 +/- 0.9 ml.kg-1.min-1, and 104.7 +/- 11.9 ml/kg, respectively. We conclude that extraction of amidated and glycine-extended gastrin-17 varies in the vascular beds, with elimination mainly confined to nonorgan tissues and the kidneys.


2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Weina Ma ◽  
Lei Lv ◽  
Jungang Guo ◽  
Yongjun Meng ◽  
Yinghua Wang ◽  
...  

The aim of this study was to examine whether Xuesaitong, a multiherbal formulation for coronary heart disease, alters the pharmacokinetics of losartan. Adult male Sprague Dawley rats randomly received losartan (10 mg/kg) or losartan plus Xuesaitong (10 mg/kg) through an oral gavage (n = 6). Multiple blood samples were obtained for up to 36 h to determine the concentrations of losartan and its active metabolite, EXP3174, through ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Pharmacokinetics were estimated using a noncompartmental model. The half-life (t1/2) of losartan was decreased by Xuesaitong (4.26 ± 1.51 vs. 6.35 ± 2.10 h; P<0.05). The apparent volume of distribution (Vd) of losartan was also decreased by the combination of losartan and Xuesaitong (4.41 ± 1.61 vs. 7.20 ± 2.41 mL; P<0.05). The time to maximum concentration (Tmax) of losartan was increased by Xuesaitong (1.06 ± 1.04 vs. 0.13 ± 0.05 h; P<0.05). Xuesaitong also decreased the t1/2 of EXP3174 (8.22 ± 1.41 vs. 6.29 ± 1.38 h; P<0.05). These results suggest that there is a complex interaction between losartan and Xuesaitong. In addition to enhanced elimination of losartan and EXP3174, Xuesaitong may also decrease the absorption rate and Vd of losartan.


1984 ◽  
Vol 3 (6) ◽  
pp. 497-503 ◽  
Author(s):  
P.-A. Hals ◽  
D. Jacobsen

1 Plasma levels of levomepromazine and two of its major metabolites N-desmethyl-levomepromazine and levomepromazine sulphoxide were studied in two poisoned patients treated with resin haemoperfusion at a constant blood flow of 200 ml/min. 2 The mean haemoperfusion clearance of levomepromazine, N-desmethyl-levomepromazine and levomepromazine sulphoxide was 114, 123 and 151 ml/min, respectively, in patient no. 1, and 153, 148 and 184 ml/min, respectively, in patient no. 2. Patient no. 2 had also ingested amitriptyline, and the mean haemoperfusion clearance of amitriptyline and its metabolite nortriptyline was 183 and 183 ml/min respectively. 3 Haemoperfusion did not seem to alter the elimination profile of levomepromazine or the two metabolites in either patient. 4 We conclude that haemoperfusion is of little value in removing levomepromazine, N-desmethyl-levomepromazine or levomepromazine sulphoxide from the body. This is probably due to the large apparent volume of distribution and the high intrinsic hepatic metabolic clearance of these compounds.


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