Effect of amiodarone on non-deiodinative pathway of thyroid hormone metabolism

1990 ◽  
Vol 122 (2) ◽  
pp. 249-254 ◽  
Author(s):  
Ram Kannan ◽  
Inder J. Chopra ◽  
Murad Ookhtens ◽  
Bramah N. Singh
Keyword(s):  
Production Rate ◽  
Clearance Rate ◽  
Area Under The Curve ◽  
Fold Increase ◽  
Molar Ratio ◽  
Metabolic Clearance ◽  
Clearance Rates ◽  
Experimental Conditions ◽  
Daily Production ◽  
Thyroid Hormone Metabolism

Abstract Amiodarone, an iodine containing anti-arrhythmic drug, causes a significant decrease in molar ratio of daily production rates of T3 and T4 from 0.75 in controls to 0.36 in amiodarone-treated rabbits. A model was constructed from the above data which showed that metabolism of T4 via non-deiodinative pathways (e.g. tetraiodothyroacetic acid and/or conjugates) increased from 29% in untreated controls to 66% in amiodarone-treated rabbits. In this study, we have examined the metbolic clearance rate of tetraiodothyroacetic acid in rabbits given amiodarone (20 mg·kg−1·day−1 ip for 3 weeks) or saline (controls). Serum amiodarone and desethylamiodarone levels under the above experimental conditions were 0.20±0.067 and 0.17±0.058 mg/l, respectively, which were in the near-therapeutic range observed in humans. Control and amiodarone-treated rabbits were administered [125I]-tetraiodothyroacetic acid (10 μCi/rabbit) iv and blood was collected at 0.5, 1, 2, 4, 6, 10, 32 and 48 h. Serum tetraiodothyroacetic acid radioactivity was determined by trichloroacetic acid precipitation and ethanol extraction and metabolic clearance rates were calculated from the area under the curve of computer fits to tetraiodothyroacetic acid radioactivity data. Amiodarone treatment decreased metabolic clearance rates significantly from 0.107 ± 0.008 in controls to 0.074 ± 0.009 1/day in amiodarone-treated rabbits (p<0.05). However, when expressed per unit body weight (1·day−1·kg−1), the metabolic clearance rates were not significantly different between the controls and amiodarone-treated rabbits. The terminal serum elimination half-life in the two groups were similar (32.0 ± 6.7 h in controls vs 49.2 ± 12.4 h in amiodarone-treated). Our data suggest that a modest decrease in clearance rate and an increased production rate could result in an increase in serum tetraiodothyroacetic acid levels which may contribute to the reduction in 5'-monodeiodination of iodothyronines documented previously in amiodarone-treated animals. The marginal decrease in metabolic clearance rate of tetraiodothyroacetic acid found in this study suggests that the two-fold increase in the conversion of T4 metabolism to non-deiodinated metabolites/conjugates in amiodarone-treated rabbits results predominantly from an increase in production rate of tetraiodothyroacetic acid.

Production rate, metabolic clearance rate and blood concentration of progesterone in conscious and anaesthetized pregnant rats

1984 ◽  
Vol 102 (3) ◽  
pp. 357-363 ◽  
Author(s):  
B. J. Waddell ◽  
N. W. Bruce
Keyword(s):  
Production Rate ◽  
Clearance Rate ◽  
Blood Concentration ◽  
Constant Infusion ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Short Term ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Anaesthetized Rats

ABSTRACT Both production rate and metabolic clearance rate (MCR) of progesterone may vary rapidly and so effect short-term changes in blood concentration of the hormone. Here, a constant infusion and sampling technique was used to estimate these three characteristics of progesterone metabolism in seven conscious and ten anaesthetized rats on day 16 of pregnancy. After steady state was achieved, four samples were collected during a 1-h period from each rat. Mean values for production rate and MCR of progesterone in conscious rats were 14·0 ±1·4 μmol/day and 63·2 ± 6·2 litres/day respectively. Both values were substantially reduced in anaesthetized rats (8.6 ±0·8 μmol/ day and 39·4± 3·4 litres/day respectively) and so blood concentration was unchanged. The production rate was positively related to the total mass of luteal tissue (common correlation coefficient, r = 0·61, P <0·05). There were no consistent changes in the three characteristics with time but variation within rats was high. The estimated coefficients of variation for production rate, MCR and blood concentration within rats were 26, 18 and 17% in conscious and 27, 20 and 23% in anaesthetized rats respectively. Short-term changes in production rate and MCR generally were in the same direction (P <0·05). This reduced variation in blood concentration which would otherwise have occurred if production rate and MCR were unrelated. The pregnant rat is clearly capable of rapid shifts in production rate, MCR and blood concentration of progesterone and the positive relationship between production rate and MCR has a homeostatic effect on blood concentration. J. Endocr. (1984) 102, 357–363

ADRENAL FUNCTION IN BREAST CANCER: PRODUCTION AND METABOLIC CLEARANCE RATE OF CORTISOL IN PATIENTS WITH EARLY OR ADVANCED BREAST CANCER AND IN NORMAL WOMEN *

1968 ◽  
Vol 42 (3) ◽  
pp. 425-432 ◽  
Author(s):  
V. JENSEN ◽  
N. DESHPANDE ◽  
R. D. BULBROOK ◽  
T. W. DOOUSS
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Cancer Patients ◽  
Production Rate ◽  
Clearance Rate ◽  
Advanced Breast ◽  
Metabolic Clearance ◽  
Breast Cancer Patients ◽  
Metabolic Clearance Rate ◽  
Significant Difference

SUMMARY The production rate of cortisol in patients with early or advanced breast cancer was compared with that of controls of comparable age. The miscible pool of this hormone was raised in advanced breast-cancer patients due to a higher production rate. The plasma clearance of cortisol remained unaffected, resulting in a higher titre of cortisol (both total and unbound) in advanced breast-cancer patients. There was no significant difference in the production rate between the early breast-cancer cases and controls. The binding of cortisol to transcortin was studied in all cases. The amount of unbound cortisol was raised in advanced breast-cancer cases. There was a significant correlation between both total and unbound cortisol and the production rate of this hormone. The latter correlation suggests that there is no abnormality in the hepatic extraction of cortisol in these patients. The metabolic clearance rate was found to be of the order of the blood flow through the liver when unbound cortisol was used for its estimation, showing that it is the unbound cortisol which is removed by the liver.

A primed-infusion technique for rapid estimation of the metabolic clearance rate of 1,25(OH)2D3

1987 ◽  
Vol 253 (3) ◽  
pp. E246-E250
Author(s):  
R. Eastell ◽  
B. L. Riggs ◽  
R. Kumar
Keyword(s):  
Production Rate ◽  
Clearance Rate ◽  
Human Subjects ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Study Interval ◽  
Normal Women ◽  
Infusion Technique

We have developed a rapid primed-infusion technique for the measurement of the metabolic clearance and production rate of 1,25-dihydroxyvitamin D3 in normal human subjects and experimental animals. With this method, an estimate of the metabolic clearance rate of 1,25-dihydroxyvitamin D3 can generally be made within 3 to 4 h. Initial studies in five dogs using 1,25-[3H]-dihydroxyvitamin D3 (180 Ci/mmol) allowed us to determine the optimal ratio of loading dose to infusion rate that resulted in the most rapid attainment of steady-state levels of plasma radioactivity. By use of this technique we found that the metabolic clearance rate of 1,25-dihydroxyvitamin D3 in dogs was 6.3 +/- 1.2 ml/min (mean +/- SD); the production rate of the hormone was 0.40 +/- 0.25 microgram/day (20.4 +/- 14.4 ng . kg-1 . day-1). In eight normal women, aged 28-51 yr, the metabolic clearance rate for 1,25-dihydroxyvitamin D3 was 25.9 +/- 4.7 ml/min; the production rate was 1.38 +/- 0.45 microgram/day (20.7 ng . kg-1 . day-1). The advantages of this method relative to ones used in the past are that it can be performed quickly (generally within 3-4 h) with the use of only tracer amounts of this hormone (equivalent to 1.1% of the production rate). With this method, no assumptions about the most appropriate model to which to fit the data need to be made. Because of its rapidity, no metabolites of the injected 1,25-dihydroxyvitamin D3 are formed during the study interval.

Production rate, metabolic clearance rate and uterine extraction of corticosterone during rat pregnancy

1994 ◽  
Vol 143 (1) ◽  
pp. 183-190 ◽  
Author(s):  
B J Waddell ◽  
H C Atkinson
Keyword(s):  
Production Rate ◽  
Clearance Rate ◽  
Statistical Significance ◽  
Blood Levels ◽  
Additional Contribution ◽  
Metabolic Clearance ◽  
Maternal Weight ◽  
Metabolic Clearance Rate ◽  
Pregnant Rats ◽  
Conscious Rats

Abstract This study examined changes in the blood concentration of corticosterone with the onset and progression of pregnancy in the rat. To identify the source of variation in blood corticosterone, the metabolic clearance rate (MCR) and production rate of corticosterone were also determined. Measurements were made in conscious rats (n=4–7 per group) in the morning of dioestrus and days 5, 10, 16 and 22 of pregnancy (term=day 23). Corticosterone levels were 713 ±38 nmol/l (mean±s.e.m.) in non-pregnant rats, remained unchanged to day 10 of pregnancy, then increased to 1036 ± 52 nmol/l by day 16 and remained high at day 22. The production rate of corticosterone appeared to increase during pregnancy from 25·6±1·7 μmol/day on day 10 to reach 36·3±3·3 mol/day on day 22, but this did not reach statistical significance (one-way ANOVA). The MCR of corticosterone was similar among all groups (overall mean 34·6±2·5 1/day), although a slight but non-significant fall was apparent at day 16. When account was taken of changes in maternal weight, the MCR decreased progressively from 139± 10 1/day per kg before pregnancy to reach a minimum of 88 ±7 1/day per kg on day 16. Transuterine extraction of corticosterone on day 22 of pregnancy was 19·2±3·1% and so, based on this and estimates of uterine blood flow, the uterus must account for around 15% of corticosterone clearance at this time. Because this uterine contribution is effectively additional clearance, it is likely that without it the MCR of corticosterone would have fallen during pregnancy. Administration of ACTH (1–24) (3·5 nmol) increased the production rate of corticosterone at dioestrus and at day 16 of pregnancy, but this effect was less marked in the pregnant group (134% and 41% increase respectively). The MCR of corticosterone also rose (17%) following ACTH(1–24) administration in pregnant but not dioestrous rats. This difference in the MCR response is likely to reflect pregnancy-induced changes in the relative levels of corticosterone, progesterone and corticosteroid-binding globulin. In conclusion, this study shows that blood levels of corticosterone increase progressively during pregnancy in conscious rats. This increase apparently resulted from the net effects of increased production and decreased MCR, neither of which reached statistical significance. It would appear, however, that the trend toward increased production of corticosterone contributes more to the rise in blood corticosterone than does MCR, since the latter was more effectively maintained at pre-pregnancy levels. The demonstration of significant transuterine extraction of corticosterone at day 22 suggests that the maintenance of corticosterone clearance late in pregnancy is due, in part, to an additional contribution by the uterus and its contents. Journal of Endocrinology (1994) 143, 183–190

scholarly journals Metabolic clearance rate and production rate of calcitriol in uremia

1989 ◽  
Vol 35 (3) ◽  
pp. 860-864 ◽  
Author(s):  
Adriana Dusso ◽  
Silvia Lopez-Hilker ◽  
Jane Lewis-Finch ◽  
Patricia Grooms ◽  
Alex Brown ◽  
...  
Keyword(s):  
Production Rate ◽  
Clearance Rate ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate

THE RELATIONSHIP OF THE SPLANCHNIC, HEPATIC AND RENAL CLEARANCE RATES TO THE METABOLIC CLEARANCE RATE OF CORTISOL IN CONSCIOUS SHEEP

1973 ◽  
Vol 56 (2) ◽  
pp. 285-294 ◽  
Author(s):  
B. A. PANARETTO ◽  
J. Y. F. PATERSON ◽  
F. HILLS
Keyword(s):  
Renal Clearance ◽  
Plasma Flow ◽  
Clearance Rate ◽  
Metabolic Clearance ◽  
Clearance Rates ◽  
Metabolic Clearance Rate ◽  
Flow Rates ◽  
Conscious Sheep ◽  
Relationship Of ◽  
The Relationship

SUMMARY The uptake of cortisol by organs in the splanchnic area of conscious, undisturbed sheep was estimated before and during the administration of adrenocorticotrophic hormone (ACTH) by measuring cortisol concentration differences in portal and hepatic venous plasma and estimating hepatic plasma flow rates. Metabolic clearance rates (MCR) of plasma cortisol were measured simultaneously. The total splanchnic clearance of cortisol was 61% of MCR in the animal, 48% being accounted for by the liver. When ACTH was given there were increases in MCR and these were accompanied by proportional increases in hepatic plasma flow rates. When ACTH was infused the total splanchnic clearance rate was 65% of MCR, 52–59% being accounted for by the liver. In other experiments the renal clearance rate of cortisol was studied. Under control conditions, and when ACTH was given, the renal clearance was 11% of MCR. The relationship of the sum of individual clearances to MCR is compared and discussed.

METABOLIC CLEARANCE RATES OF PREGNENOLONE, 17-ACETOXYPREGNENOLONE AND THEIR SULPHATE ESTERS IN MAN AND IN RABBIT

1967 ◽  
Vol 39 (3) ◽  
pp. 395-403 ◽  
Author(s):  
D. Y. WANG ◽  
R. D. BULBROOK ◽  
F. ELLIS ◽  
M. M. COOMBS
Keyword(s):  
Clearance Rate ◽  
Metabolic Clearance ◽  
Dehydroepiandrosterone Sulphate ◽  
Clearance Rates ◽  
Metabolic Clearance Rate ◽  
Free Steroid

SUMMARY The metabolic clearance rates, distribution volumes and half-lives of pregnenolone, 17-acetoxypregnenolone and their sulphate esters were determined in man and in the rabbit. Pregnenolone was cleared about three times more quickly than pregnenolone sulphate in both species. The metabolic clearance rate of 17-acetoxypregnenolone sulphate is greater in the rabbit than in man, whether expressed in absolute terms or in relation to the metabolic clearance rate of the free steroid. The slow clearance rate of 17-acetoxypregnenolone sulphate in man is similar to that of testosterone sulphate, dehydroepiandrosterone sulphate and cholesterol sulphate; but is unlike that of pregnenolone sulphate, which is cleared approximately ten times as quickly.

Pharmacokinetics of norethindrone acetate in women after the insertion of a single subdermal implant releasing norethindrone acetate

1982 ◽  
Vol 99 (2) ◽  
pp. 302-308 ◽  
Author(s):  
Harbans Singh ◽  
J P Uniyal ◽  
P Jha ◽  
D Takker ◽  
K Murguesan ◽  
...  
Keyword(s):  
Production Rate ◽  
Clearance Rate ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Significant Change ◽  
Continuous Presence ◽  
Norethindrone Acetate ◽  
Subdermal Implant

Abstract. The metabolic clearance rate (MCR) of norethindrone acetate1 (NETA) and norethindrone (NET) levels in plasma were studied after an iv injection of [3H]NETA in three women before and at 1 week, 1, 2 and 6 months following the insertion of a single silastic subdermal implant releasing microquantities of NETA. No significant change in the MCR of NETA was observed at 1 week (459 ± 72 1/day), 1 month (489 ± 113 1/day) and 2 months (522 ± 144 1/day) compared with that of control (525 ± 108 1/day). However, MCR of NETA showed significant increase in women exposed to continuous presence of NETA for a period of 6 months (608 ± 121 1/day; P < 0.025). NETA was rapidly and extensively metabolized into NET. At 1 week, 1, 2 and 6 months of study, NET was observed to be present in higher amounts compared with NETA. The production rate (PR) of progesterone decreased significantly at 2 and 6 months of NETA implant insertion compared with the PR before the insertion of implant.

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