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.

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.

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.

Pharmacokinetics of Prilocaine after Intravenous Administration in Volunteers 

1999 ◽  
Vol 90 (4) ◽  
pp. 988-992 ◽  
Author(s):  
Auke Dirk van der Meer ◽  
Anton G. L. Burm ◽  
Rudolf Stienstra ◽  
Jack W. van Kleef ◽  
Arie A. Vletter ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
High Performance ◽  
Equilibrium Dialysis ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Unbound Fraction ◽  
Blood Samples ◽  
The Mean ◽  
The Difference

Background Prilocaine exists in two stereoisomeric configurations, the enantiomers S(+)- and R(-)-prilocaine. The drug is clinically used as the racemate. This study examined the pharmacokinetics of the enantiomers after intravenous administration of the racemate. Methods Ten healthy male volunteers received 200 mg racemic prilocaine as a 10-min intravenous infusion. Blood samples were collected for 8 h after the start of the infusion. Plasma concentrations were measured by stereoselective high-performance liquid chromatography (HPLC). Unbound fractions of the enantiomers in blank blood samples, spiked with racemic prilocaine, were determined using equilibrium dialysis. Results The unbound fraction of R(-)-prilocaine (mean +/- SD, 70%+/-8%) was smaller (P &lt; 0.05) than that of S(+)-prilocaine (73%+/-5%). The total plasma clearance of R(-)-prilocaine (2.57+/-0.46 l/min) was larger (P &lt; 0.0001) than that of S(+)-prilocaine (1.91+/-0.30 l/min). The steady-state volume of distribution of R(-)-prilocaine (279+/-94 l) did not differ from that of S(+)-prilocaine (291+/-93 l). The terminal half-life of R(-)-prilocaine (87+/-27 min) was shorter (P &lt; 0.05) than that of S(+)-prilocaine (124+/-64 min), as was the mean residence time of R(-)-prilocaine (108+/-30 min) compared with S(+)-prilocaine (155+/-59 min; P &lt; 0.005). Conclusions The pharmacokinetics of prilocaine are enantioselective. The difference in clearance is most likely a result of a difference in intrinsic metabolic clearance. The difference in the pharmacokinetics of the enantiomers of prilocaine does not seem to be clinically relevant.

METABOLIC CLEARANCE RATE, PRODUCTION RATE, AND MAMMARY UPTAKE AND METABOLISM OF PROGESTERONE IN COWS

1975 ◽  
Vol 66 (2) ◽  
pp. 239-247 ◽  
Author(s):  
R. B. HEAP ◽  
A. HENVILLE ◽  
J. L. LINZELL
Keyword(s):  
Production Rate ◽  
Clearance Rate ◽  
Jugular Vein ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Tracer Kinetic ◽  
The Mean ◽  
Jersey Cows ◽  
Conscious Animals ◽  
Uptake And Metabolism

SUMMARY Tracer kinetic techniques have been used to measure the production rate, metabolic clearance rate and mammary uptake of progesterone in six experiments on two Jersey cows. The cows were surgically prepared so that the carotid artery, jugular vein and mammary vein concentrations of progesterone, and udder blood flow, could be determined in conscious animals without anaesthesia or stress. The mean production rate of progesterone was 173 ± 23·3 (s.e.m.) μg/min, with values ranging from 80 to 276 μg/min in pregnancy. The metabolic clearance rate was 22·5 ± 2·0 1/min, or 0·21 ± 0·025 1/min/kg metabolic body weight. The mammary uptake of progesterone was low, 3·1 ± 1·1 μg/min, and udder uptake accounted for about 3% of progesterone production rate. During [3H]progesterone infusion, radioactivity was transferred from blood to milk, probably by diffusion down a concentration gradient. Progesterone accounted for more than 88% of the ether-soluble radioactivity recovered from milk.

Metabolic clearance rate of testosterone in male epileptic patients on anti-convulsant therapy

1991 ◽  
Vol 129 (3) ◽  
pp. 465-468 ◽  
Author(s):  
M. J. Wheeler ◽  
B. K. Toone ◽  
A. Dannatt ◽  
P. B. C. Fenwick ◽  
S. Brown
Keyword(s):  
Clearance Rate ◽  
Patient Population ◽  
Free Testosterone ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Testosterone Concentration ◽  
The Mean ◽  
Low Testosterone

ABSTRACT There are several reports which state that male epileptics on anti-convulsant therapy have reduced sexual activity. We and others have shown that, although total testosterone is raised, the free testosterone concentration is reduced in this patient population. This could be a result of an increased metabolic clearance rate (MCR) of testosterone, inadequate secretion of LH to stimulate testosterone synthesis or inappropriately low testosterone production by the Leydig cells. We have examined these possibilities by measuring the MCR of testosterone in 15 male epileptics on anti-convulsant therapy. In this group of patients, the mean LH (9·3±5·9 IU/l) and sex-hormone binding globulin (SHBG) (54·5±22·9 nmol/l) concentrations were significantly greater than those of five normal control subjects (4·7±1·11 IU/l and 26·0 ±7·0 nmol/l respectively). Mean total testosterone concentrations of the two groups were not significantly different but the mean percentage of free testosterone and free testosterone concentration were significantly lower in the patient population (2·06±0·43 vs 2·98±0·27 and 0·56±1·1 vs 0·79±0·7 pmol/l). The MCR of testosterone was significantly lower in the patients (773±322 vs 1354±443 1/day) and showed a positive correlation with the percentage of free testosterone. Therefore, our results suggest that the lowered free testosterone in male epileptics on anti-convulsant therapy is not due to an increased MCR of testosterone. The increased LH concentration suggests primary hypogonadism. This, in turn, could be responsible for low free testosterone levels in the presence of normal testosterone. Journal of Endocrinology (1991) 129, 465–468

Characterization of somatostatin in peripheral and portal plasma in the duck: in-vivo metabolism of somatostatin-28 and-14

1984 ◽  
Vol 100 (3) ◽  
pp. 329-335 ◽  
Author(s):  
D. Di Scala-Guenot ◽  
M.-T. Strosser ◽  
P. Mialhe
Keyword(s):  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Peripheral Plasma ◽  
Specific Radioimmunoassay ◽  
Extraction Step ◽  
Portal Plasma ◽  
The Mean ◽  
Somatostatin 14

ABSTRACT A sensitive and specific radioimmunoassay without an extraction step was developed for somatostatin in duck plasma. Degradation of Tyr1-125I-labelled somatostatin-14 (S-14) averaged 2% for blood collected with EDTA and zymofren. Recovery of somatostatin-like immunoreactivity (SLI), added to the plasma, averaged 91% for S-14 and 86% for S-28. Chromatographic analysis of portal plasma on Sephadex G-25 showed three peaks: one peak coeluted with cytochrome c (mol. wt 12 500) in the void volume and was called 'big' somatostatin; of the two smaller forms, one coeluted with synthetic S-28 and the other with synthetic S-14; these were immunologically and physicochemically indistinguishable from synthetic S-28 and S-14. In peripheral plasma only the large form of somatostatin, 'big' somatostatin, was found. The mean portal plasma concentration of SLI was 4·1 ±0·41 μg/l (n = 11, range 2·8–5·1 μg/l). In peripheral plasma the SLI concentration was 1·05 ±0·45 μg/l (n = 11, range 0·84–1·2 μg/l). The metabolic clearance rate, distribution volume and calculated half-life values were 63·1 ± 14 ml/kg per min, 40·9±8·9 ml/kg and 1·06±0·19 min for S-14 compared with 45·7 ±7 ml/kg per min, 14·8 ±2·5 ml/kg and 2·14± 0·54 min for S-28. These results indicated that S-28 was cleared from plasma at a slower rate than S-14 in the duck. It was concluded that: (1) portal plasma SLI was four times higher than peripheral SLI; (2) SLI in portal plasma existed as 'big' somatostatin, S-28 and S-14, whereas in peripheral plasma it existed mainly as 'big' somatostatin; (3) invivo studies indicated that S-28 was metabolized less rapidly than S-14. J. Endocr. (1984) 100, 329–335

Metabolic clearance rate of arginine vasopressin in severe chronic renal failure

1992 ◽  
Vol 83 (5) ◽  
pp. 583-587 ◽  
Author(s):  
Nicholas B. Argent ◽  
Robert Wilkinson ◽  
Peter H. Baylis
Keyword(s):  
Renal Failure ◽  
Steady State ◽  
Chronic Renal Failure ◽  
Arginine Vasopressin ◽  
Clearance Rate ◽  
Plasma Concentrations ◽  
Normal Subjects ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Plasma Arginine

1. The metabolic clearance rate of arginine vasopressin was determined using a constant infusion technique in normal subjects and patients with chronic renal failure immediately before commencing dialysis. Endogenous arginine vasopressin was suppressed in all subjects before the infusion with a water load. 2. Plasma arginine vasopressin concentrations were determined using a sensitive and specific radioimmunoassay after Florisil extraction. The detection limit of the assay was 0.3 pmol/l, and intra- and inter-assay coefficients of variation at 2 pmol/l were 9.7% and 15.3%, respectively. 3. In normal subjects, the metabolic clearance rate was determined at two infusion rates producing steady-state concentrations of arginine vasopressin of 1.3 and 4.4 pmol/l. In the patients with renal failure, a single infusion rate was used, producing a steady-state concentration of 1.5 pmol/l. 4. At comparable plasma arginine vasopressin concentrations, metabolic clearance rate was significantly reduced in patients with renal failure (normal 1168 ± 235 ml/min versus renal failure 584 ± 169 ml/min; means ± sd; P<0.001). 5. Free water clearance was significantly reduced in normal subjects during the arginine vasopressin infusion from 8.19 ± 2.61 to −1.41 ± 0.51 ml/min (P<0.001), but was unchanged in the patients with renal failure after attaining comparable plasma arginine vasopressin concentrations. 6. In normal subjects there was a small but significant fall in metabolic clearance rate at the higher steady-state arginine vasopressin concentration (1168 ± 235 ml/min at 1.3 pmol/l versus 1059 ± 269 ml/min at 4.4 pmol/l; P = 0.016). 7. Our results show that the metabolic clearance rate of arginine vasopressin is reduced by approximately 50% in severe chronic renal failure. This alone may account for the raised plasma concentrations of the hormone seen in this condition.

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