Sex Differences in the Metabolism of Ethanol and Acetaldehyde in Normal Subjects

1984 ◽  
Vol 67 (4) ◽  
pp. 397-401 ◽  
Author(s):  
M. J. P. Arthur ◽  
A. Lee ◽  
R. Wright
Keyword(s):  
Sex Differences ◽  
Elimination Rate ◽  
Young Male ◽  
Normal Subjects ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Mean Value ◽  
The Mean ◽  
Ethanol Elimination ◽  
Apparent Volume Of Distribution

1. Blood ethanol and acetaldehyde concentrations were compared in normal young male and female subjects after intravenous infusion of 0.5 g of ethanol/kg body weight. 2. After the infusion was completed, females had significantly higher mean concentrations of blood ethanol than males, but a significantly lower apparent volume of distribution (Vd) of ethanol (0.56 ± 0.06 l/kg vs 0.68 ± 0.17 l/kg, P<0.05). There were no differences in ethanol elimination rate (EER) (females 1.78 ± 0.3 mmol h−1 kg−1; males 1.87 ± 0.41 mmol h−1 kg−1). The mean value of the areas under the acetaldehyde/time curves (AUC) were significantly greater for males (88.5 ± 26.4 μmol/l. h) than for females (58.6 ± 31.5 μmol/l. h, P<0.05). 3. Since the ethanol elimination rate was similar in both sexes, the observed differences in AUC for acetaldehyde may reflect the sex differences in metabolism of this substrate by the liver.

Letters to the Editor

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 ◽  
...  
Keyword(s):  
Elimination Rate ◽  
Area Under The Curve ◽  
Compartment Model ◽  
Apparent Volume ◽  
Systemic Circulation ◽  
Volume Of Distribution ◽  
Letters To The Editor ◽  
Correct Formula ◽  
Original Report ◽  
Apparent Volume Of Distribution

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

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.

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.

Estimation of Pharmacokinetic Parameters at Steady-State in Patients

1978 ◽  
Vol 12 (10) ◽  
pp. 612-616 ◽  
Author(s):  
James W. Crow ◽  
Milo Gibaldi
Keyword(s):  
Steady State ◽  
Rate Constant ◽  
Elimination Rate ◽  
Simulated Data ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Total Clearance ◽  
Dosing Intervals ◽  
Apparent Volume Of Distribution

A method to characterize the pharmacokinetics of a drug in a patient receiving it chronically is proposed. In principle, such characterization may be carried out by obtaining one or more drug concentration in plasma-time values from several different dosing intervals, combining the data to create a composite dosing interval representative of the steady-state situation and fitting the data to an appropriate equation. The method was evaluated using simulated data based on the average pharmacokinetic parameters of theophylline in children. Reasonable estimates of the elimination rate constant and apparent volume of distribution may be obtained, but the estimation of the absorption rate constant presents formidable problems. The method appears to be most useful for obtaining very accurate estimates of total clearance.

Metabolism and influence of gastrin-52 on gastric acid secretion in humans

1995 ◽  
Vol 269 (4) ◽  
pp. G600-G605 ◽  
Author(s):  
C. P. Hansen ◽  
F. Stadil ◽  
J. F. Rehfeld
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Normal Subjects ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Gel Chromatography ◽  
A Minor ◽  
Apparent Volume Of Distribution

It has been shown recently that the two largest alpha-carboxyamidated progastrin products are gastrin-71 and gastrin-52. Human gastrin-52 has now been synthesized, and the effect on gastric acid secretion and elimination from plasma was examined and compared with gastrin-17 in 12 normal subjects. The peptides were infused separately in four consecutive doses; the maximum response of gastrin-17 and gastrin-52 was 25.2 +/- 2.8 and 22.2 +/- 2.8 mmol H+/50 min, respectively (P< 0.01). This difference in efficacy was presumably related to nonequilibrium of gastrin-52 between plasma and receptor. The elimination of gastrin-17 was monoexponential with a half-life of 4.7 +/- 0.3 min; clearance and apparent volume of distribution were 16.7 +/- 1.5 ml.kg-1.min-1 and 106.0 +/- 9.2 ml/kg, respectively. The elimination of gastrin-52 was biexponential, the half-lives were 4.9 +/- 0.7 and 49.9 +/- 4.2 min, and clearance and apparent volume of distribution were 1.9 +/- 0.2 ml.kg-1.min-1 and 106.3 +/- 10.1 ml/kg, respectively. Gel chromatography of plasma samples drawn during infusion of gastrin-52 revealed that most of the immunoreactivity eluted in the position of the intact peptide. Small peaks in the positions of gastrin-34 and the NH2-terminal pentapeptide fragment of gastrin-52 indicate that a minor part of gastrin-52 is degraded to smaller peptides in vivo. It is concluded that gastrin-52 is bioactive with an efficacy close to or similar to that of gastrin-17. A minor fraction of gastrin-52 undergoes postsecretory cleavage either in plasma or after capillary transit.

scholarly journals Studies on effects of lactose on experimental Trypanosoma vivax infection in Zebu cattle. 1. Plasma kinetics of intravenously administered lactose at onset of infection and pathology

2008 ◽  
Vol 75 (2) ◽  
Author(s):  
M. Y. Fatihu ◽  
S. Adamu ◽  
I. A. Umar ◽  
N. D.G. Ibrahim ◽  
L. O. Eduvie ◽  
...  
Keyword(s):  
Muscular Atrophy ◽  
Elimination Rate ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Zebu Cattle ◽  
Trypanosoma Vivax ◽  
Histopathological Lesions ◽  
The Mean ◽  
Total Body

Lactose in normal saline was administered intravenously to a group of Zebu cattle infected with Trypanosoma vivax to determine the bloodplasma kinetics at onset of an experimental infection and its ability to protect tissues against damage as part of preliminary studies to determine its suitability for use in the treatment of trypanosomosis. Significant (P <0.01) higher lactose concentrations were observed in the T. vivax-intecled bulls at 30 min and 1h (P< 0.05) post-infectio (p.i.) and by 4 h p.i. the plasma lactose remained above the level prior to infusion, after which it fell slightly below the preinfusion level in the uninfected group. Calculated pharmacokinetic parameters revealed delayed excretion of lactose in the T. vivax-intected group soon after infection. The total body clearance (C/B )was significantly (P < 0.05) reduced. The biological half-life (t1/2), elimination rate constant (kel) and apparent volume of distribution (Vd) were relatively decreased (P > 0.05) as a result of the T. vivax infection. Retention of lactose in the plasma was attributed to decreased plasma clearance l.t is suggested that the presence of trypanosomes in circulation rather than organic lesions could have been responsible for the delay observed in the excretion of lactose.At 12 weeks p.i., when the experiment was terminated, the group infected and given lactose infusion (despiteh igherp arasitaemia) had no gross or histopathological lesions in the brain, spleen, lymphnodes, heart, kidneys, liver and testes. However, the group infected but not infused with lactose were emaciated, had pale mucosae, watery blood, general muscular atrophy, serous atrophy of coronary fat and other adiposet issue, hepatomegalys, plenomegalys, wollen and oedematous lymph nodes, all of which are suggestive of trypanosomosis. Histopathological lesions included arrowing of Bowman's space and hypercellularity of glomerular tufts in the kidneys with the mean glomerula truft nucleairn dices (GTNs) in the group significantly higher (P <0.01)than the mean GTNs of the lactoseinfused and control bulls. Degenerative changes occurred in the myocardium, spleen, testes and epididymides. The tesicular and epididymal lesions are indicative of male reproductive dysfunction.

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.

Antipyrine Metabolism in African Villagers

1985 ◽  
Vol 4 (4) ◽  
pp. 379-384 ◽  
Author(s):  
K. Sommers ◽  
D.A. van Staden ◽  
J. Moncrieff ◽  
H.S. Schoeman
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
Antipyrine Clearance ◽  
Serum Samples ◽  
Mean Values ◽  
Pakistani Immigrants ◽  
Serial Serum ◽  
The Mean ◽  
Apparent Volume Of Distribution ◽  
Mixed Function Oxidase Activity

1 Antipyrine clearance has been measured from serial serum samples in 49 healthy black Africans from a village in Southern Africa. 2 The subjects follow a lifestyle which minimally exposes them to environmental inducing or inhibiting agents. Food is mainly maize cereal, with a protein content of only about 8.8%, together with greens. 3 Antipyrine clearance, half-life and apparent volume of distribution (mean ± SD) were, respectively, 0.538 ± 0.163 ml min-1 kg-1, 14.81 ± 6.5 h and 0.626 ± 0.075 litre/kg. These results do not differ significantly from the mean values found in a group of lactovegetarian Indo-Pakistani immigrants to Britain. 4 This would suggest that the major environmental determinant influencing hepatic mixed-function oxidase activity is the presence or absence of meat in the diet. However, the relative contributions of environment and heredity will be difficult to determine.

Safety of a Higher Loading Dose of Phenobarbital in the Term Newborn

PEDIATRICS ◽  
1985 ◽  
Vol 75 (6) ◽  
pp. 1061-1064 ◽  
Author(s):  
Steven M. Donn ◽  
Thaddeus H. Grasela ◽  
Gary W. Goldstein
Keyword(s):  
Newborn Infants ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Loading Dose ◽  
Cardiorespiratory Function ◽  
Term Newborns ◽  
The Mean ◽  
Spontaneously Breathing ◽  
Apparent Volume Of Distribution

The conventional loading dose of phenobarbital for newborn infants with hypoxic-ischemic seizures, 20 mg/kg, often fails to control convulsive activity. To determine the safety of a higher loading dose and to establish the pharmacokinetic parameters of a higher loading dose, ten severely asphyxiated term newborns were given 30 mg/kg of phenobarbital intravenously over 15 minutes. The mean serum concentration of phenobarbital two hours after loading was 30.0 ± 3.2 µg/mL, the apparent volume of distribution was 0.97 ± 0.18 L/kg, total clearance was 0.08 ± 0.03 mL/min/kg, and mean serum half-life was 148 ± 55 hours. The higher loading dose was not associated with any short-term adverse effects on cardiorespiratory function, even in spontaneously breathing infants.

Metabolism and acid secretory effect of sulfated and nonsulfated gastrin-6 in humans

2000 ◽  
Vol 279 (5) ◽  
pp. G903-G909 ◽  
Author(s):  
C. Palnæs Hansen ◽  
F. Stadil ◽  
J. F. Rehfeld
Keyword(s):  
Clearance Rate ◽  
Main Product ◽  
Acid Output ◽  
Normal Subjects ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Apparent Volume Of Distribution

The antral hormone gastrin is synthesized by processing progastrin into different peptides that stimulate gastric secretion. The effect on acid secretion depends mainly on the metabolic clearance rate of the peptides, but some of them may differ in potency and maximum acid output at similar concentrations in plasma. Sulfated and nonsulfated gastrin-6 are the smallest circulating bioactive gastrins in humans. Their effect and metabolism have now been investigated in nine normal subjects and compared with nonsulfated gastrin-17, a main product of progastrin. Maximum acid output after stimulation with gastrin-17, sulfated gastrin-6, and nonsulfated gastrin-6 were 28.3 ± 2.0, 24.5 ± 2.0 ( P < 0.02), and 19.3 ± 2.3 ( P < 0.05) mmol H+/50 min, respectively, and the corresponding EC50values were 43 ± 6, 24 ± 2 ( P < 0.01), and 25 ± 2 (not significant) pmol/l. The half-life of gastrin-17 was 5.3 ± 0.3 min, the metabolic clearance rate (MCR) was 16.5 ± 1.3 ml · kg−1· min−1, and the apparent volume of distribution (Vd) was 124.3 ± 9.6 ml/kg. The half-lives of sulfated and nonsulfated gastrin-6 were 2.1 ± 0.3 and 1.9 ± 0.3 min, the MCRs were 42.8 ± 3.7 and 139.4 ± 9.6 ml kg−1min−1( P < 0.01), and the Vdwere 139.0 ± 30.5 and 392.0 ± 81.6 ( P < 0.01) ml kg−1. All pharmacokinetic parameters differed significantly from gastrin-17 ( P < 0.01). We conclude that gastrin 6 has a higher potency but a lower efficacy than gastrin-17. The efficacy of gastrin-6 is increased by tyrosine O-sulfation, which also enhances the protection against elimination.

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