The influence of disulfiram on the half life and metabolic clearance rate of diphenylhydantoin and tolbutamide in man

1976 ◽  
Vol 9 (5-6) ◽  
pp. 439-441 ◽  
Author(s):  
T. Lysbo Svendsen ◽  
M. Brandt Kristensen ◽  
J. M�lholm Hansen ◽  
L. Skovsted
Keyword(s):  
Clearance Rate ◽  
Half Life ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate

Comparative metabolic clearance rate, volume of distribution and plasma half-life of human β-lipotropin and acth

Life Sciences ◽  
1978 ◽  
Vol 23 (23) ◽  
pp. 2323-2330 ◽  
Author(s):  
Anthony S. Liotta ◽  
Choh Hao Li ◽  
George C. Schussler ◽  
Dorothy T. Krieger
Keyword(s):  
Clearance Rate ◽  
Half Life ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Plasma Half Life

Fate of circulating renin in conscious rats

1987 ◽  
Vol 252 (1) ◽  
pp. E136-E146 ◽  
Author(s):  
S. Kim ◽  
H. Iwao ◽  
N. Nakamura ◽  
F. Ikemoto ◽  
K. Yamamoto
Keyword(s):  
Clearance Rate ◽  
Half Life ◽  
High Performance ◽  
Slow Component ◽  
High Performance Liquid Chromatographic ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Conscious Rats ◽  
Liver And Kidney ◽  
Liquid Chromatographic

Highly purified 125I-labeled rat renal renin (125I-renin) was given intravenously to conscious rats to study the fate of circulating renin. Specific antirat renin antiserum was used to identify the labeled renin molecules. In sham-operated rats, the disappearance of 125I-renin from the plasma showed two exponential components with a half-life of 6.7 +/- 0.4 min for the rapid component and 65.1 +/- 5.7 min for the slow component. The metabolic clearance rate was 11.4 +/- 1.0 ml X min-1 X kg-1. In bilaterally nephrectomized rats, the metabolic clearance rate of 125I-renin was reduced by 55%, but the half-life of the slow component remained unchanged. Seventy percent hepatectomy caused a 54% decrement in the metabolic clearance and prolonged the half-life of the slow component. Five minutes after injection of 125I-renin, approximately 59 and 11% of the administered 125I-renin had accumulated in the liver and the kidneys, respectively, and at later time points the 125I-renin was highly concentrated in these organs. High-performance liquid chromatographic analysis of the liver and kidney extracts demonstrated that 125I-renin was catabolized by these organs. Biliary excretion of 125I-renin was negligible. Urinary excretion of 125I-renin up to 120 min was approximately 2% of the injected dose. We conclude that both the liver and the kidney are responsible for the clearance of circulating renin, with participation of the liver being predominant.

Physiology of 24,25-dihydroxyvitamin D3 in normal human subjects

1982 ◽  
Vol 243 (5) ◽  
pp. E370-E374 ◽  
Author(s):  
R. Kumar ◽  
R. Wiesner ◽  
M. Scott ◽  
V. L. Go
Keyword(s):  
Production Rate ◽  
Biliary Excretion ◽  
Clearance Rate ◽  
Half Life ◽  
Human Subjects ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Dihydroxyvitamin D3 ◽  
Normal Human ◽  
24,25 Dihydroxyvitamin D3

We determined the metabolic clearance and production rates of 24,25-dihydroxyvitamin D3 in four normal healthy adults. We also examined the excretion of radioactivity in stool, urine, and bile after the intravenous administration of 24,25-[3H]dihydroxyvitamin D3 to human subjects. 24,25-Dihydroxyvitamin D3 is rapidly cleared from the plasma with a half-life of approximately 390 +/- 25 min (mean +/- SE). The metabolic clearance rate of 24,25-dihydroxyvitamin D3 was 9.2 +/- 1.5 liters/day with a production rate of 26.4 +/- 7.2 micrograms/day (mean +/- SE). Within 1 day 13.0 +/- 4.2% (mean +/- SE) of the administered dose had appeared in the stool; by day 7, 48.8 +/- 2.7% of the dose had appeared in the feces. Within 24 hr, 6.4 +/- 0.8% of the administered dose appeared in the urine; 7.4 +/- 1.8% of the dose had appeared in the urine within 2 days. The biliary excretion of 24,25-dihydroxyvitamin D3 was studied in two subjects. By 8 h, 15.3 +/- 1.3% of the administered dose had appeared in the bile. The metabolites present in bile, feces, and urine were much more polar than 24,25-dihydroxyvitamin D3. These results demonstrate that 24,25-dihydroxyvitamin D3 is rapidly cleared from plasma and is excreted in the feces (probably via the bile) and urine of normal human subjects.

Pharmacokinetics and organ-specific metabolism of calcitonin gene-related peptide in sheep

1988 ◽  
Vol 118 (1) ◽  
pp. 25-31 ◽  
Author(s):  
K. G. Braslis ◽  
A. Shulkes ◽  
D. R. Fletcher ◽  
K. J. Hardy
Keyword(s):  
Steady State ◽  
Clearance Rate ◽  
Half Life ◽  
Calcitonin Gene Related Peptide ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Related Peptide ◽  
Modes Of Action ◽  
Calcitonin Gene ◽  
Organ Specific

ABSTRACT Calcitonin gene-related peptide (CGRP) is a product of the calcitonin gene with a widespread distribution in neural tissue of the brain, gut and perivascular nerves. Infusion of CGRP produces multiple biological effects, but the physiological significance of these findings will be influenced by the sites and rates of CGRP metabolism. The metabolic clearance rate and half-life of disappearance of human CGRP were estimated in conscious sheep after infusing CGRP at 1 or 5 pmol/kg per min to steady-state conditions. The particular organs involved in the clearance of CGRP were assessed by measuring the inflow and outflow concentrations across the liver, gut, kidney, lung and brain. The metabolic clearance rate at steady state was 22·6 ± 2·1 (s.e.m.) and 15·0±1·7 ml/kg per min for the 1 and 5 pmol/kg per min doses respectively. The half-life of disappearance was bi-exponential: 3·6±0·3 min for the first phase and 13·6±1·0 min for the second phase. High-pressure liquid chromatography of plasma at equilibrium revealed only a single peak coeluting with CGRP(1–37): no immunoreactive metabolites were detected. These pharmacokinetic values are intermediate between that of a neurotransmitter and a hormone and are therefore consistent for a peptide with both circulatory and neurotransmitter modes of action. The kidney, with an arterial–renal vein gradient of 14%, and the liver, with a portal– hepatic vein gradient of 25%, were the major organs involved in the clearance of CGRP. The specific organ clearance, however, accounted for only one-third of the whole body metabolic clearance rate of CGRP, suggesting that other more generalized degradative systems are involved, such as endothelial-bound enzymes of blood vessels. This information on clearance and organ-specific metabolism should form a basis for evaluating the physiological roles and modes of action of CGRP. J. Endocr. (1988) 118,25–31

Degradation of 125I-labelled prolactin in the rabbit: effect of nephrectomy and prolactin infusion

1983 ◽  
Vol 99 (3) ◽  
pp. 369-377 ◽  
Author(s):  
I. R. Falconer ◽  
A. T. Vacek
Keyword(s):  
Clearance Rate ◽  
Half Life ◽  
Chronic Renal Disease ◽  
Degradation Products ◽  
Metabolic Clearance ◽  
Plasma Prolactin ◽  
Exogenous Hormone ◽  
Metabolic Clearance Rate ◽  
Liver And Kidney ◽  
Ovine Prolactin

Hyperprolactinaemia in patients with chronic renal disease undergoing dialysis has prompted the investigation of the relative roles of liver and kidney in the degradation of prolactin. Male rabbits were acutely nephrectomized, and compared with intact animals with or without prolactin infusion. Prolactin degradation was followed after intravenous injection of 125I-labelled ovine prolactin. Measurements were made of peptide-bound 125I and 125I-labelled degradation products in plasma, liver, kidney, bile, urine and muscle and total thyroid radioactivity. A significant (P<0·01) reduction in the metabolic clearance rate of 125I-labelled prolactin was observed due to nephrectomy, with double the accumulation of 125I-labelled peptides in the livers in this group. Prolactin infusion of nephrectomized animals had a further and larger effect than nephrectomy alone on prolactin degradation. Metabolic clearance rate significantly (P<0·01) decreased from 5·5 ml/min per kg in nephrectomized rabbits to 0·8 ml/min per kg with prolactin infusion. The accumulation of 125I-labelled prolactin degradation products in the blood was significantly (P<0·01) lower in this group of animals and the amount of peptide-bound 125I in plasma at 60 min after 125I-labelled prolactin administration was significantly (P<0·01) higher. Liver degradation of prolactin in the absence of exogenous hormone appears to be sufficient to maintain an approximately normal half-life for prolactin in plasma (intact t½ = 6·8 min; nephrectomized t½ = 8·5 min). However, with prolactin infusion the half-life of 125I-labelled prolactin increased to 28·5 min, and the plasma prolactin concentrations measured by radioimmunoassay rose linearly with time. These data supported the view that hyperprolactinaemia associated with renal dysfunction is substantially due to hormone oversecretion.

Sign in / Sign up

Export Citation Format

Share Document