Resin Haemoperfusion in Levomepromazine Poisoning: Evaluation of Effect on Plasma Drug and Metabolite Levels

1984 ◽  
Vol 3 (6) ◽  
pp. 497-503 ◽  
Author(s):  
P.-A. Hals ◽  
D. Jacobsen
Keyword(s):  
Blood Flow ◽  
Plasma Levels ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
The Body ◽  
Metabolic Clearance ◽  
Plasma Drug ◽  
The Mean ◽  
Apparent Volume Of Distribution

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.

Ketamine kinetics: decerebrate vs. intact cats

1979 ◽  
Vol 57 (8) ◽  
pp. 878-881 ◽  
Author(s):  
James E. Heavner ◽  
Duane C. Bloedow
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
Drug Dose ◽  
The Body ◽  
Pharmacokinetic Parameters ◽  
Peripheral Compartment ◽  
Blood Concentrations ◽  
Open Model ◽  
Apparent Volume Of Distribution ◽  
Compartment Open Model

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.

Relationship Between Dose and Apparent Volume of Distribution of Salicylate in Children

PEDIATRICS ◽  
1974 ◽  
Vol 54 (6) ◽  
pp. 713-717
Author(s):  
Gerhard Levy ◽  
Sumner J. Yaffe
Keyword(s):  
Salicylic Acid ◽  
Time Course ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
The Body ◽  
Method Of Calculation ◽  
Salicylate Concentration ◽  
Peritoneal Dialysis Fluid ◽  
Salicylate Intoxication ◽  
Apparent Volume Of Distribution

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.

Pharmacokinetics and organ metabolism of carboxyamidated and glycine-extended gastrins in pigs

1996 ◽  
Vol 271 (1) ◽  
pp. G156-G163 ◽  
Author(s):  
C. P. Hansen ◽  
F. Stadil ◽  
L. Yucun ◽  
J. F. Rehfeld
Keyword(s):  
Clearance Rate ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Constant Rate Infusion ◽  
Constant Rate ◽  
Vascular Beds ◽  
Apparent Volume Of Distribution ◽  
Rate Infusion

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.

PHARMACOKINETICS OF EN0XAPARIN AFTER SINGLE SUBCUTANEOUS ADMINISTRATION OF INCREASING DOSES (20 UP TO 80 MG) TO HEALTHY VOLUNTEERS

1987 ◽  
Author(s):  
L Bara ◽  
Y Le Roux ◽  
M Woler ◽  
F Chauliac ◽  
A Frydman ◽  
...  
Keyword(s):  
Subcutaneous Administration ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Thrombin Time ◽  
Mean Values ◽  
Elimination Half ◽  
Heparin Plasma ◽  
The Mean ◽  
The One ◽  
Apparent Volume Of Distribution

The pharmacokinetics of enoxaparin (E) was randomly studied in 12 healthy male volunteers. Each dose (20-40-60 and 80 mg) was injected via subcutaneous (sc) route with a one-week wash out period. Anti-Xa and anti-IIa activities (ACT), calcium thrombin time (CTT) and Heptest were measured over a 36 hour period. E and the IV th International Heparin Standard were both used as internal standards.The anti IIa and CTT effects were only measurable when the injected dose was higher than 40 mg. The maximum anti-Xa and anti-IIa ACT were obtained 3 to 4 hours after the dose. As anti-IIa ACT is lower than anti-Xa ACT (anti-Xa/anti-IIa ACT ration I .6 to 2), the complete pharmacokinetic description of E was only based on anti-Xa data. Thus, the mean values of the maximal anti-Xa ACT (A max) were respectively: 1.58 ± 0.35 pg/ml; 3.83 ± 0.98 jig/ml, 5.38 ± 0.75 ug/ml and 7.44 ± 1.4 pg/ml for the four doses (20-40-60 and 80 mg). The resorption of E after sc injection was strictly linear whereas the relationships between A max or AUC in the one hand and dose in the other hand were A (anti Xa) Max = 0.0954 (dose) - 0,2083 r = 0.9146/p < 0.001; n = 48) and AUC (0 - 36 h) = 0.9117 (dose) - 7.59 (r = 0.9133/p < 0.001; n = 48). The mean residence time of E was close to 6 h (5.83 ± 0.86 h for D = 40 mg; 6.19 ± 0.74 h for D = 60 mg and 6.44 ± 0.76 h for 80 mg) indicating that around 50% of the total anti Xa ACT is induced in a 6 hour interval. The apparent volume of distribution V is close to 61 (6.59 1 ±1.33 1 for D = 60 mg) and the total Dody clearance is equal to 1.25 1/h, indicating the rate of depolymerisation of enoxaparin is lower than that of heparin. Plasma elimination half-life of anti-Xa ACT is equal to 4.36 ± 1.07 h (D = 40 mg) whereas that of anti-IIa ACT is shorter, fi) = 2.1 h). These results indicate that enoxaparin exhibits i) a differential anti-Xa/anti-IIa ACT profile, ii) a linear relationship between dose and anti-Xa/anti-IIa ACT and iii) a kinetic profile which is significantly different from that of standard heparin.

EFFECTS OF ACUTE NEUROTROPHIC STRESS ON PERIPHERAL METABOLISM OF CORTISOL IN CONSCIOUS MALE GUINEA-PIGS

1981 ◽  
Vol 89 (3) ◽  
pp. 443-449 ◽  
Author(s):  
M. MANIN ◽  
P. DELOST
Keyword(s):  
Adult Male ◽  
Guinea Pigs ◽  
Binding Capacity ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Control Value ◽  
Cortisol Metabolism ◽  
Free Cortisol ◽  
The Mean

Cortisol metabolism was studied in conscious adult male guinea-pigs subjected to a neurotrophic stress (immobilization and stimulation by light for 3 h). The disappearance curves of tracer quantities of [3H]cortisol were represented by a two-pool model. In stressed animals, there was a marked increase in the mean plasma level of cortisol (184% of control value; P <0·001) and in the metabolic clearance rate (MCR; 17% of control value; 0·001 <P <0·01). This rise in the MCR of plasma cortisol resulted from an increase in the mean total apparent volume of distribution (49%, P < 0·001). The lack of significant differences in the slopes of the second exponential phase of the disappearance curves indicated that the stress did not significantly increase the half-life of cortisol. The mean binding capacity of transcortin for cortisol (ST) was significantly higher in the animals which had been subjected to the neurotrophic stress than in the control guinea-pigs (0·02 < P <0·05). However, ST values remained very low and accounted for the very high levels of free cortisol found after the stress. The results suggest that the raised concentrations of unbound cortisol found in the plasma of conscious adult male guinea-pigs in response to neurotrophic stress reflect a hypersecretion of corticosteroid.

Model of the distribution and metabolism of a GnRH superagonist in dogs

1990 ◽  
Vol 258 (3) ◽  
pp. E468-E475
Author(s):  
D. Lacoste ◽  
B. Candas ◽  
M. Normand ◽  
F. Labrie
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
Gonadotropin Releasing Hormone ◽  
Metabolic Clearance ◽  
Sigmoid Function ◽  
Subcutaneous Route ◽  
Metabolic Clearance Rate ◽  
Fractional Rate ◽  
Kinetics Of ◽  
Apparent Volume Of Distribution

The plasma kinetics of [D-Trp6, des-Gly-NH2(10)]gonadotropin-releasing hormone (GnRH) ethylamide was assessed in eight dogs over a period of 8 h after rapid intravenous or subcutaneous injection. Each animal received doses of 0.2, 2, and 20 micrograms/kg body wt iv and 1 and 10 micrograms/kg body wt sc. A two-compartment structure, to which a source compartment was added to represent the subcutaneous route, adequately fits the five kinetics when the apparent volume of distribution follows a plasma concentration-dependent sigmoid function. Despite the nonlinearity, the apparent volume of distribution can be approximated by a constant value of 280 ml/kg body wt for the dynamics corresponding to the three lowest and more physiological doses. The metabolic clearance rate is 4.63 ml.min-1.kg body wt-1. The two exponential components that characterize the two-compartment structure are equal to 0.0348 +/- 0.0053 and 0.00470 +/- 0.00060 min-1, respectively. The agonist injected subcutaneously diffuses to plasma at a fractional rate of 0.0265 +/- 0.0029 min-1. Disposal occurs at a maximal rate of 0.017 and 0.0055 min-1 of the amount of agonist present in the central and peripheral compartments, respectively. The highest fractional exchange rate between compartments reaches 0.01 min-1. As simulated with the model, a continuous infusion of 4.63 ng.min-1.kg body wt-1 leads to a steady state of 1 ng/ml plasma; 90% of that level is reached 7 h after the onset of the subcutaneous input signal. The kinetics of plasma [D-Trp6, des-Gly-NH2(10)]GnRH ethylamide is many times slower than that of the native hormone and of the other GnRH agonists.

Sex-Related Differences In Aspirin Pharmacokinetics Following IV Injection In Rabbits

1981 ◽  
Author(s):  
M R Buchanan ◽  
J Rosenfeld ◽  
J Hirsh
Keyword(s):  
Plasma Levels ◽  
Arterial Thrombosis ◽  
Vessel Wall ◽  
Experimental Studies ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Antithrombotic Agent ◽  
Platelet Accumulation ◽  
Serial Samples ◽  
Apparent Volume Of Distribution

Clinical and experimental studies suggest that aspirin (ASA) is a useful antithrombotic agent; however, its efficacy seems limited to males. This may be due to differences in i) the effects of ASA on platelets and/or vessel wall or ii) the pharmacokinetics of ASA, between males and females.We examined the possible sex-related differences in 1) enhanced arterial thrombosis 3 h after treatment with 0, 3, 10 or 100 mg/kg ASA and 2) the distribution (α) and clearance (β) of ASA between male and female rabbits. Enhanced arterial thrombosis was determined by measuring 51Cr-platelet accumulation onto injured carotid arteries. ASA-plasma levels were determined, using a GC/MS assay. 51Cr-platelet accumulation onto injured arteries was 0.67 ± 0.15 × 106 (males) and 0.52 ± 0.07 × 106/100 mm2 vessel wall (females; mean ± SEM, n=8). 3 mg/kg ASA had no effect. 10 and 100 mg/kg ASA significantly enhanced 5lcr- platelet accumulation to 1.94 ± 0.41 × 106 and 2.59 ± 0.93 × 106 in males, and to 1.65 ± 0.32 × 106 and 2.16 ± 0.73 × 106 in females (p<0.001). There were no sex-related differences.ASA-plasma levels were determined in serial samples collected from 10 rabbits injected with 10 mg/kg ASA. One week later, the study was repeated in the same animals. The α and β T½’s were 3.3 ± 0.2 and 29.2 ± 3.0 (min) respectively in males after the 1st treatment. Similar T½’s were found after the 2nd treatment (3.4 ± 0.1, 23.3 ± 3.5 respectively). In females, the initial α and β T½’s were 3.7 ± 0.2 and 26.1 ± 3.5 respectively. The α T½ was similar (3.6 ± 0.1) whereas the β T½ was significantly decreased (14.8 ± 0.3, p<0.007) after the 2nd ASA treatment. This decrease in females was associated with an increase in the apparent volume of distribution, p<0.02The significance of these findings is uncertain.

Effect of Pesticide Exposure on Human Microsomal Enzyme Induction

1982 ◽  
Vol 1 (2) ◽  
pp. 155-158 ◽  
Author(s):  
R. Uppal ◽  
P.R. Sharma ◽  
R.R. Chaudhury
Keyword(s):  
Half Life ◽  
Pesticide Exposure ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Microsomal Enzymes ◽  
Metabolic Clearance Rate ◽  
Apparent Volume Of Distribution ◽  
Microsomal Enzyme Induction ◽  
Hepatic Microsomal Enzymes

1 The antipyrine half-life, metabolic clearance rate and the apparent volume of distribution were measured in six subjects handling malathion. These results were compared with six appropriate controls. 2 Occupational exposure of malathion in subjects reduced the antipyrine half-life from 9.18 ± 2.16 h in controls to 4.73 ± 1.65 h. 3 It is concluded that malathion exposure increases the rate of antipyrine elimination, possibly by inducing the hepatic microsomal enzymes.

scholarly journals Pharmacokinetics and Ex Vivo Pharmacodynamic Antimalarial Activity of Dihydroartemisinin-Piperaquine in Patients with Uncomplicated Falciparum Malaria in Vietnam

2009 ◽  
Vol 53 (8) ◽  
pp. 3534-3537 ◽  
Author(s):  
Dao Van Hoang Nguyen ◽  
Quoc Phuc Nguyen ◽  
Ngoa Dang Nguyen ◽  
Thuy Thi Thanh Le ◽  
The Duy Nguyen ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Body Weight ◽  
Healthy Subjects ◽  
Antimalarial Activity ◽  
Ex Vivo ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Oral Clearance ◽  
The Mean ◽  
Apparent Volume Of Distribution

ABSTRACT Compared to healthy subjects, malaria patients show a reduction in the mean oral clearance (1.19 versus 5.87 liters/h/kg of body weight) and apparent volume of distribution (1.47 versus 8.02 liters/kg) of dihydroartemisinin in Vietnamese patients following treatment with dihydroartemisinin-piperaquine (Artekin) for uncomplicated Plasmodium falciparum. Dihydroartemisinin is responsible for most of the ex vivo antimalarial activity of dihydroartemisinin-piperaquine.

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