KINETICS OF 3H-TESTOSTERONE METABOLISM IN PATIENTS WITH CARCINOMA OF THE PROSTATE: EFFECTS OF OESTROGEN ADMINISTRATION

1971 ◽  
Vol 67 (4) ◽  
pp. 733-739 ◽  
Author(s):  
C. E. Bird ◽  
R. N. Green ◽  
R. S. Calandra ◽  
J. G. Connolly ◽  
A. F. Clark
Keyword(s):  
Beneficial Effect ◽  
Clearance Rate ◽  
Prostatic Carcinoma ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Oestrogen Therapy ◽  
Metabolic Clearance Rate ◽  
Testosterone Metabolism ◽  
Kinetics Of ◽  
Volumes Of Distribution

ABSTRACT We studied the effects of oestrogen administration on the kinetics of testosterone metabolism in patients with prostatic carcinoma. We investigated changes in the metabolic clearance rate, transport and metabolic rate constants and volumes of distribution. In all patients but one, the metabolic clearance rate and volumes of distribution were low during oestrogen administration. The beneficial effect of oestrogen therapy in patients with prostatic carcinoma may be related to the increase in the rate of testosterone metabolism (K2) within a smaller volume of distribution (V1).

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

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.

Incremental and decremental kinetics of gastric responses to infused gastrin in dogs

1982 ◽  
Vol 242 (6) ◽  
pp. G660-G667
Author(s):  
B. I. Hirschowitz
Keyword(s):  
Volume Of Distribution ◽  
Blood Levels ◽  
Published Data ◽  
Gastric Fistula ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Molar Basis ◽  
Human Gastrin ◽  
The Right ◽  
Kinetics Of

Acid and pepsin secretion was stimulated by graded doses of synthetic human gastrin I (G-17-I) and pentagastrin (G-5) in six conscious gastric fistula dogs, three with intact vagi and three with fundic vagotomy. Metabolic clearance rate of G-17 was 15.2 ml.kg-1.min-1 and volume of distribution was 15.8%. Gastrin levels decayed in two slopes: t1/2 of 6.8 min and 25-35 min, respectively. These were compared with other published data. Vmax was higher in intact stomachs and at doses or blood levels of gastrin about three to four times smaller. G-17 was almost four times more potent (molar basis) than G-5. Responses were log linearly related to G-17 dose and to serum G-17 during infusion (incremental) and after stopping infusion (decremental). Normalized decremental curves were congruent in all dogs but displaced fivefold (625 vs. 130 pmol/l) to the right at midpoint. Vagotomy changed only association (incremental) kinetics (Km = 352 pmol/l). The previously undescribed difference between blood concentration-effect relationship during drug administration and withdrawal may be important in situations in which blood levels are used as therapeutic guide.

The Kinetics of Plasma Noradrenaline in Normal and Hypertensive Subjects

1978 ◽  
Vol 55 (s4) ◽  
pp. 89s-92s ◽  
Author(s):  
S. Ghione ◽  
C. Palombo ◽  
M. Pellegrini ◽  
E. Fommei ◽  
A. Pilo ◽  
...  
Keyword(s):  
Clearance Rate ◽  
Normal Subjects ◽  
Plasma Noradrenaline ◽  
Metabolic Clearance ◽  
Venous Sampling ◽  
Metabolic Clearance Rate ◽  
Hypertensive Patients ◽  
Arterial Blood ◽  
Endogenous Noradrenaline ◽  
Kinetics Of

1. The kinetics of plasma noradrenaline have been determined in normal and essential hypertensive patients by intravenous injection of tritiated noradrenaline and serial mixed venous sampling. 2. The metabolic clearance rate of plasma noradrenaline in normal subjects was approximately 1·1 min−1 m−2, whereas in essential hypertensive patients it was significantly reduced to approximately 0·61 min−1 m−2. 3. Metabolic clearance rate was negatively correlated to mean arterial blood pressure and total peripheral resistances. 4. Particularly low values of metabolic clearance rate were found in two patients with congestive heart failure and one with phaeochromocytoma. 5. We propose that the access of plasma noradrenaline to the main removal mechanisms takes place in competition with the flow of unlabelled endogenous noradrenaline directly released by nerve endings. The slower removal of plasma noradrenaline in essential hypertension could then express a larger release of endogenous noradrenaline in this condition.

Metabolic clearance rate in sheep of a met-enkephalin analogue estimated by radioimmunoassay

1982 ◽  
Vol 93 (3) ◽  
pp. 427-433 ◽  
Author(s):  
J. E. Bolton ◽  
J. H. Livesey ◽  
R. A. Donald
Keyword(s):  
Clearance Rate ◽  
Bolus Injection ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Time Intervals ◽  
Naturally Occurring ◽  
Specific Radioimmunoassay ◽  
The Mean

A sensitive and specific radioimmunoassay developed for measuring the met-enkephalin analogue d-ala2-met(0)5-ol-enkephalin (DAMME) was used to study the pharmacokinetics of DAMME in the circulation of sheep. Plasma concentrations of DAMME were measured at varying time-intervals after an intravenous bolus injection or following a constant intravenous infusion of the analogue. The mean metabolic clearance rate of DAMME was 2·8 ml/min per kg, the mean circulating half-life was 52 min and the mean volume of distribution was 190 ml/kg. The longer circulating time of the analogue when compared with that of naturally occurring met-enkephalin would appear to explain its prolonged analgesic effect.

scholarly journals Effect of pregnancy on the metabolic clearance rate and the volume of distribution of oxytocin in the baboon

1998 ◽  
Vol 274 (5) ◽  
pp. E791-E795 ◽  
Author(s):  
Wlodzimierz B. Kowalski ◽  
Lubomir Diveky ◽  
Ramkrishna Mehendale ◽  
Michael Parsons ◽  
Laird Wilson
Keyword(s):  
Clearance Rate ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Arterial Access ◽  
Initial Dilution ◽  
Uterine Contractions ◽  
The Mean ◽  
Dilution Volume

Pharmacokinetic parameters of oxytocin (OT) metabolism were determined during the last third of pregnancy and again 4–8 wk after delivery in the baboon. Animals were placed on a tether system with venous and arterial access and a continuous monitoring of uterine contractions during gestation. Two methods of determining OT pharmacokinetics were utilized (bolus injection vs. continuous infusion). The metabolic clearance rate of OT as determined during the bolus trials ( n = 7) was 22.2 ± 1.5 ml ⋅ min−1 ⋅ kg−1in pregnancy and 16.3 ± 1.4 ml ⋅ min−1 ⋅ kg−1postpartum ( P < 0.05), respectively, and 23.7 ± 2.8 vs. 16.9 ± 3.7 ml ⋅ min−1 ⋅ kg−1( P < 0.05), respectively, as determined during the 1-h infusion trials ( n = 4). The initial dilution volume and the volume of distribution at steady state of OT after administration did not differ between pregnant and postpartum animals ( P > 0.05). The mean residence time (MRT) of OT was shorter during pregnancy, 7.7 ± 0.8 vs. 10.8 ± 1.2 min postpartum ( P < 0.05). In summary, OT metabolism during pregnancy in the baboon is characterized by 1) increased clearance rate (1.4-fold), 2) accelerated turnover due to the shorter MRT, and 3) unaltered distribution.

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.

The metabolism of gastrin-52 and gastrin-6 in pigs

2000 ◽  
Vol 279 (3) ◽  
pp. G552-G560 ◽  
Author(s):  
C. Palnæs Hansen ◽  
J. P. Goetze ◽  
F. Stadil ◽  
J. F. Rehfeld
Keyword(s):  
Clearance Rate ◽  
Half Life ◽  
Bolus Injection ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Organ Specific ◽  
Differential Elimination ◽  
Apparent Volume Of Distribution

The kinetics and metabolism in various organs of three bioactive products of progastrin, the small sulfated and nonsulfated gastrin-6 and the large nonsulfated gastrin-52, were examined during intravenous administration in anesthetized pigs. The kidney, hindlimb, liver, head, and gut eliminated the hexapeptides efficiently, with a fractional extraction ranging from 0.50 to 0.28 ( P < 0.001–0.05). No metabolism was recorded in the lungs, and sulfation was without influence on the extraction of gastrin-6. Gastrin-52 was eliminated only in the kidney and the head, with a fractional extraction between 0.23 and 0.11 ( P < 0.01–0.05). The half-life of sulfated and nonsulfated gastrin-6 was 1.5 ± 0.4 and 1.4 ± 0.3 min, the metabolic clearance rate (MCR) was 80.8 ± 7.6 and 116.0 ± 13.5 ml · kg−1· min−1( P < 0.05), and the apparent volume of distribution (Vdss) was 199.3 ± 70.1 and 231.4 ± 37.3 ml/kg, respectively. The decay of gastrin-52 in plasma was biexponential. The half-lives of this biexponential after a bolus injection were 3.9 ± 0.5 ( T1/2α) and 25.7 ± 1.4 ( T1/2β) min, and the MCR and Vdsswere 4.2 ± 0.4 ml · kg−1· min−1and 116.2 ± 16.2 ml/kg1. We conclude that there is a differential elimination of progastrin products in splanchnic and nonsplanchnic tissue, which depends on the chain length of the peptides. Sulfation of gastrin-6 had no influence on the organ-specific extraction but reduced the MCR. Our results are in keeping with previous studies of nonsulfated gastrin-17, which is extracted in the kidney, head, limb, and gut but not in the liver.

BLOOD AND URINE CLEARANCE OF LUTEINIZING HORMONE RELEASING HORMONE IN MAN MEASURED BY RADIOIMMUNOASSAY

1974 ◽  
Vol 60 (2) ◽  
pp. 305-314 ◽  
Author(s):  
S. L. JEFFCOATE ◽  
R. H. GREENWOOD ◽  
D. T. HOLLAND
Keyword(s):  
Luteinizing Hormone ◽  
Clearance Rate ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Production Rates ◽  
Metabolic Clearance Rate ◽  
Daily Production ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Lh Rh

SUMMARY The clearance of synthetic luteinizing hormone releasing hormone (LH-RH) after intravenous injection has been investigated in man. Thirteen tests were performed in ten subjects, four of whom were normal, the other six had proven disease of the hypothalamo-pituitary region. The rate of disappearance of LH-RH from the circulation could be represented as a double exponential with half-times of the two components of 5·3 and 27·4 min respectively. The initial volume of distribution was 11·1 ± 1·6 (s.d.) 1 and the metabolic clearance rate 1480 ± 170 (s.d.) 1/day. There was no difference in any of these parameters between normal and abnormal subjects. Between 0·75 and 2·8% of the injected dose was excreted in the urine within 8 h, of which 48% was excreted in the first hour. The daily production rates of LH-RH were calculated from the urinary excretion rates; these gave higher results than production rates calculated from the blood metabolic clearance rate. Possible reasons for this are discussed.

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