Structure-kinetic relationships of choriogonadotropin and related molecules

1989 ◽  
Vol 256 (6) ◽  
pp. E721-E724
Author(s):  
L. Liu ◽  
J. L. Southers ◽  
J. W. Cassels ◽  
S. M. Banks ◽  
R. E. Wehmann ◽  
...  
Keyword(s):  
Rate Constants ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Clearance Rates ◽  
Glycoprotein Hormone ◽  
Core Fragment ◽  
Initial Volume ◽  
Human Choriogonadotropin ◽  
Pregnancy Urine ◽  
Volumes Of Distribution

To assess how profound differences in carbohydrate and/or polypeptide structures affect parameters of plasma disappearance of glycoprotein hormones, we calculated and compared the initial volume of distribution, rate constants, and metabolic clearance rates of several highly purified human choriogonadotropin (hCG) analogues in monkeys. hCG, deglycosylated hCG, desialylated hCG, or core fragment of hCG-beta purified from pregnancy urine (beta-core) was administered as a rapid intravenous injection to adult male cynomolgus monkeys (n = 3/group). The metabolic clearance rates of deglycosylated hCG, beta-core fragment, and desialylated hCG were increased 15-, 47-, and 152-fold, respectively, over that of hCG. Their corresponding initial volumes of distribution, however, remained essentially unchanged compared with that of hCG and approximated the estimated plasma volume. In contrast, the fast and slow rate constants of plasma disappearance of the hCG analogues were increased as much as 18- and 23-fold, respectively, relative to those of hCG. These studies of structure-kinetic relationships in primates show that major carbohydrate and polypeptide modifications of a glycoprotein hormone cause profound changes in the rate constants of the disappearance curves without changes in the initial volume of distribution.

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).

Studies on the mechanism of the selective suppression of plasma levels of follicle-stimulating hormone in the female rat after administration of steroid-free bovine follicular fluid

1983 ◽  
Vol 97 (3) ◽  
pp. 327-338 ◽  
Author(s):  
W. J. de Greef ◽  
F. H. de Jong ◽  
J. de Koning ◽  
J. Steenbergen ◽  
P. D. M. van der Vaart
Keyword(s):  
Follicular Fluid ◽  
Plasma Levels ◽  
Single Injection ◽  
Constant Infusion ◽  
Metabolic Clearance ◽  
Female Rat ◽  
Clearance Rates ◽  
Lh Rh ◽  
Lh Releasing Hormone ◽  
Hypophysial Portal

Steroid-free bovine follicular fluid (bFF) selectively suppresses the plasma levels of FSH in the female rat, demonstrating that bFF contains inhibin-like material. The present study was concerned with the effects of bFF on the hypothalamic release of LH releasing hormone (LH-RH) into hypophysial stalk blood and on the metabolic clearance rates of gonadotrophins. The metabolic clearance rates of FSH, LH and prolactin were determined after a single injection of and during a constant infusion with adenohypophysial extract. Similar results were obtained with both methods, and treatment with bFF did not alter the metabolic clearance rates of FSH, LH and prolactin. Anaesthesia with urethane, used for surgery involved in the collection of hypophysial stalk blood, did not interfere with the effect of bFF on plasma levels of FSH. The administration of bFF did not change the hypothalamic content of LH-RH, but caused a 30% decrease in the levels of LH-RH in hypophysial stalk plasma. However, a fraction isolated from bFF, which contained 20 times more inhibin-like activity per mg protein than bFF, did not alter the hypothalamic release of LH-RH into the hypophysial portal blood while this fraction was effective in specifically suppressing the plasma levels of FSH. It was concluded that the inhibin-like activity in bFF does not suppress the plasma levels of FSH by affecting its plasma clearance or by influencing the hypothalamic release of LH-RH, but that it has a direct effect on the adenohypophysis in inhibiting the release of FSH. Besides the inhibin-like activity, bFF also contains another factor which can decrease the levels of LH-RH in hypophysial stalk plasma.

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

Metabolic Clearance Rates of Diiodotyrosine in Man

1972 ◽  
Vol 34 (4) ◽  
pp. 666-670 ◽  
Author(s):  
PETER A. SINGER ◽  
JOHN T. NICOLOFF
Keyword(s):  
Metabolic Clearance ◽  
Clearance Rates

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.

Half-life, hemodynamic, renal, and hormonal effects of prorenin in cynomolgus monkeys

1991 ◽  
Vol 260 (4) ◽  
pp. R804-R810 ◽  
Author(s):  
T. Lenz ◽  
J. E. Sealey ◽  
T. Maack ◽  
G. D. James ◽  
R. L. Heinrikson ◽  
...  
Keyword(s):  
Half Life ◽  
Renal Plasma Flow ◽  
Plasma Renin ◽  
Apparent Volume ◽  
Reproductive Organs ◽  
Volume Of Distribution ◽  
Plasma Testosterone ◽  
Metabolic Clearance ◽  
Cynomolgus Monkeys ◽  
Pharmacokinetic Properties

Prorenin is found in human plasma, kidneys, and reproductive organs. We investigated the physiological and pharmacokinetic properties of plasma prorenin, and its plasma conversion to active renin, by bolus infusions of human recombinant prorenin (0.5, 2, 20 micrograms; n = 4/dose) into anesthetized male cynomolgus monkeys. The infused prorenin had 3% intrinsic renin activity. Plasma prorenin rose from 61 +/- 6 to 101 +/- 11, 570 +/- 46, and 7,700 +/- 390 ng.ml-1.h-1, respectively, after 5 min. Plasma renin increased to 3% of total renin, angiotensin II increased less than twofold, and aldosterone did not change. Plasma testosterone fell slightly (P less than 0.01). Mean arterial pressure (MAP) fell slowly from 104 +/- 3 to 93 +/- 3 mmHg at 60 min (P less than 0.001). Heart rate, glomerular filtration rate, renal plasma flow, and urinary sodium and potassium excretion were unchanged. For the 2- and 20-micrograms doses, respectively, effective half-life of plasma decay was 47 +/- 4.9 and 109 +/- 21 min (P less than 0.05), apparent volume of distribution was 145 +/- 11 and 166 +/- 35 ml/kg, and metabolic clearance rate was 2.30 +/- 0.44 and 1.08 +/- 0.14 ml.min-1.kg-1 (P less than 0.01). In conclusion, neither the hormonal nor the physiological response to infusion of pharmacologic levels of recombinant human prorenin into monkeys provide evidence for conversion of circulating prorenin to renin. MAP did not increase and actually fell without commensurate effects on renal function. The half-life of recombinant prorenin was similar to that of renin.

Measurement of Extracellular Fluid Volume of Nephrectomized Dogs With Mannitol, Sucrose, Thiosulfate and Radiosulfate

1956 ◽  
Vol 185 (1) ◽  
pp. 179-184 ◽  
Author(s):  
Patrick J. Mulrow ◽  
Herbert M. Oestreich ◽  
Roy C. Swan
Keyword(s):  
Exponential Function ◽  
Extracellular Fluid ◽  
Volume Of Distribution ◽  
Fluid Volume ◽  
Extracellular Fluid Volume ◽  
Simple Exponential Function ◽  
Volumes Of Distribution

Volumes of distribution of mannitol, sucrose, thiosulfate and radiosulfate have been measured simultaneously in nephrectomized dogs. The volume of distribution of each substance is reproducible when the substance is reinfused 6 hours later. There appears to be no increase in the extracellular fluid volume during this interval as a result of the nephrectomy. The logarithm of the concentration of mannitol, sucrose and radiosulfate continues as a simple exponential function of time from the 3rd to 30th hour after their infusion. The volumes of distribution of mannitol and radiosulfate reflect increments in extracellular fluid with fair accuracy, while the sucrose distribution measures only 72% of a 1-liter expansion of extracellular fluid. There are serious limitations in the application of thiosulfate distribution to such measurements.

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.

Multiple cold air exposures change oral triiodothyronine kinetics in normal men

1992 ◽  
Vol 263 (1) ◽  
pp. E85-E93 ◽  
Author(s):  
H. L. Reed ◽  
M. M. D'Alesandro ◽  
K. R. Kowalski ◽  
L. D. Homer
Keyword(s):  
Cold Exposure ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Group Effect ◽  
Metabolic Clearance Rate ◽  
Free T4 ◽  
Cold Air ◽  
Normal Men ◽  
Serum Tsh

The influence of cold exposure on triiodothyronine (T3) kinetics was studied in 16 men before, during (biweekly), and after 80 (10/wk) cold (4 degrees C) air exposures. We used serum values before and up to 24 h after a pharmacological oral (o) dose of T3 [76.8 nmol (50 micrograms)] to calculate noncompartmental kinetic parameters. To assess the role of thyroxine (T4) and thyrotropin (TSH), we administered a replacement dose of T3 [46.0 nmol/day (30 micrograms)] to eight men (+T3 group) and placebo to eight others (-T3 group) for the 2-mo study. There was no group effect of T3 treatment (+T3) on oral total volume of distribution (TVdo), metabolic clearance rate (MCRo), or disposal rate (DRo). TVdo was not changed over the study. Cold increased MCRo by 5.4 +/- 2.0 l.day-1.m-2. DRo increased with cold by 10.2 +/- 4.4 nmol.day-1.m-2. Although serum TSH, total T4, and free T4 decreased by approximately 50% in the +T3 group, the changes in MCRo and DRo with cold were not different from those in -T3. We describe that human T3 kinetics are changed with brief repeated exposures to cold air and that these increases in MCRo and DRo do not appear to be dependent on TSH or T4.

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