BLOOD LEVELS OF SYNTHETIC GLUCOCORTICOIDS AFTER ADMINISTRATION BY VARIOUS ROUTES

1979 ◽  
Vol 82 (1) ◽  
pp. 149-157 ◽  
Author(s):  
YUKITAKA MIYACHI ◽  
HIDEKI YOTSUMOTO ◽  
TAKASHI KANO ◽  
AKIRA MIZUCHI ◽  
TETSUICHIRO MUTO ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Liver Disease ◽  
Oral Dose ◽  
Oral Administration ◽  
Intramuscular Injection ◽  
Peak Serum ◽  
Blood Levels ◽  
Serum Concentrations ◽  
Synthetic Glucocorticoids ◽  
Synthetic Glucocorticoid

SUMMARY Using reliable radioimmunoassay methods, the concentrations of prednisolone, prednisolone-hemisuccinate, betamethasone and betamethasone-17-benzoate were determined after administration by various routes. Serum prednisolone and betamethasone concentrations increased to peak levels 2 h after oral administration and then decreased gradually. The half-times of disappearance of prednisolone and betamethasone from blood, after a single oral dose, were both approximately 180–220 min. Five to fifteen minutes after intramuscular injections of 20 mg prednisolone-hemisuccinate the peak serum concentration was 63·7 ± 7·4 μg/ 100 ml and 30 min later plasma unesterified prednisolone reached its highest level (28·8 ± 2·6 μg/100 ml). The administration of steroids through the rectum induced gradual increases in the levels of serum steroids, reaching a maximum of 25% of the peak serum concentrations observed after oral administration. Plasma betamethasone-17-benzoate levels of 300 ng/ 100 ml were observed after topical application of betamethasone-17-benzoate gel to the skin. In patients with liver disease, the clearance of betamethasone was very slow compared with that in normal control subjects and significant amounts were retained in the blood 24 h after oral administration, showing that the liver is the most important organ for the metabolism of synthetic glucocorticoid. The concentrations of prednisolone and prednisolone-hemisuccinate in the cerebrospinal fluid were very low after the intramuscular injection of prednisolone-hemisuccinate, confirming the relative impermeability of the blood–brain barrier to polar steroids.

The bioavailability of thyroxine and 3,5,3′-triiodothyronine in normal subjects and in hyper- and hypothyroid patients

1985 ◽  
Vol 110 (4) ◽  
pp. 483-486 ◽  
Author(s):  
Kjeld Hasselström ◽  
Kaj Siersbæk-Nielsen ◽  
lb Bo Lumholtz ◽  
Jens Faber ◽  
Carsten Kirkegaard ◽  
...  
Keyword(s):  
Oral Administration ◽  
Clinical Implication ◽  
Area Under The Curve ◽  
Normal Subjects ◽  
Relative Difference ◽  
Peak Serum ◽  
New Method ◽  
Serum Concentrations ◽  
Significant Difference ◽  
Hypothyroid Patients

Abstract. A new method for the estimation of the bioavailability of thyroxine (T4) and 3,5,3′-triiodothyronine (T3) is described based on gel separation followed by antibody extraction of labelled T4 and T3 from serum, and using the area under the curve of disappearance of the tracer (AUC) for the calculations. The peak serum concentrations of radioactive labelled T4 and T3 were reached approximately 90 min after oral administration of both tracers. The relative difference of duplicate estimations was below 10% (n = 3). The bioavailability of T4 in 6 euthyroid controls was in median 65% (range 64–75%), and it was significantly increased both in hyperthyroidism (88% (75–99%), n = 6, P < 0.01) and hypothyroidism (84% (67–100%), n = 6, P<0.02). The bioavailability of T3 in 6 euthyroid controls was in median 78% (69–99%) and significantly greater than that of T4 (P < 0.02). The bioavailability was unaffected by hyperthyroidism (79% (61–98%), n = 9) and hypothyroidism (77% (66–97%), n = 7). No significant difference between T4 and T3 bioavailabilities was found in hyper- or hypothyroidism. The clinical implication of the present study is that the bioavailability of T4 and T3 is almost identical and approximately 80% in patients with severe hypothyroidism.

The Bioavailability of Orphenadrine Hydrochloride after Intramuscular and Oral Administration

1982 ◽  
Vol 10 (6) ◽  
pp. 447-450 ◽  
Author(s):  
G Rutigliano ◽  
J J M Labout
Keyword(s):  
Plasma Concentration ◽  
Oral Dose ◽  
Oral Administration ◽  
Intramuscular Injection ◽  
Dosage Form ◽  
Plasma Concentrations ◽  
Clinical Use ◽  
Unchanged Drug ◽  
Single Intramuscular Injection ◽  
Oral Doses

The bioavailability of orphenadrine hydrochloride after a single intramuscular injection was compared to that after a single oral dose by following serial plasma concentration estimations of the unchanged drug. The bioavailability of orphenadrine from the intramuscular dosage form proved to be equal to or even greater than that from the tablet. Eight subjects received 40 mg orphenadrine HCl intramuscularly and 50 mg orally on separate occasions 1 week apart. The first hour plasma concentrations after intramuscular doses were significantly higher than those after oral doses, supporting the clinical use of the intramuscular route in those indications where rapid effects of the drug are required.

Changes in growth rate and thyroid- and sex-hormones blood levels in rats under sub-chronic lithium treatment

2006 ◽  
Vol 25 (5) ◽  
pp. 243-250 ◽  
Author(s):  
M S Allagui ◽  
N Hfaiedh ◽  
C Vincent ◽  
F Guermazi ◽  
J-C Murat ◽  
...  
Keyword(s):  
Growth Rate ◽  
Lithium Treatment ◽  
Lithium Carbonate ◽  
Serum Levels ◽  
Antagonistic Effect ◽  
Blood Levels ◽  
Vaginal Mucosa ◽  
Dependent Manner ◽  
Serum Concentrations ◽  
Dose Dependent

Lithium therapy, mainly used in curing some psychiatric diseases, is responsible for numerous undesirable side effects. The present study is a contribution to the understanding of the pathophysiological mechanisms underlying lithium toxicity. Male and female mature rats were divided into three batches and fed commercial pellets: one batch was the control and the second and third batches were given 2 g (Li1) and 4 g (Li2) of lithium carbonate/kg of food/day, respectively. After 7, 14, 21 and 28 days, serum levels of free tri-iodothyronine (FT3), thyroxine (FT4), testosterone and estradiol were measured. Attention was also paid to growth rate and a histological examination of testes or vaginal mucosa was carried out. In treated rats, a dose-dependent loss of appetite and a decrease in growth rate were observed, together with symptoms of polydypsia, polyuria and diarrhea. Lithium serum concentrations increased from 0.44 mM (day 7) to 1.34 mM (day 28) in Li1 rats and from 0.66 to 1.45 mM (day 14) in Li2 rats. Li2 treatment induced a high mortality after 14 days, reaching 50-60% in female and male animals. From these data, the LD50 (14 days Li2 chronic treatment) was calculated to be about 0.3 g/day per kilogram of animal, leading to Li serum concentrations of about 1.4 mM. A significant decrease of FT3 and FT4 was observed in treated rats. This effect appeared immediately for the highest dose and was more pronounced for FT3, resulting in an increase of the FT4/FT3 ratio. In males, testosterone decreased and spermatogenesis was stopped. Conversely, in females, estradiol increased in a dose-dependent manner as the animals were blocked in the diestrus phase at day 28. This finding supports a possible antagonistic effect of lithium on the estradiol receptors.

Comparison of serum fluoride levels after administration of monofluorophosphate-calcium carbonate or sodium fluoride: differences in peak serum concentrations

1994 ◽  
Vol 72 (12) ◽  
pp. 1082-1085 ◽  
Author(s):  
L. Erlacher ◽  
H. Teufelsbauer ◽  
P. Bernecker ◽  
P. Pietschmann ◽  
M. Weissel
Keyword(s):  
Calcium Carbonate ◽  
Sodium Fluoride ◽  
Peak Serum ◽  
Serum Concentrations

Pharmacokinetics of the Antimalarial Drug, AQ-13, in Rats and Cynomolgus Macaques

2004 ◽  
Vol 23 (3) ◽  
pp. 179-189 ◽  
Author(s):  
Sandhya Ramanathan-Girish ◽  
Paul Catz ◽  
Moire R. Creek ◽  
Benjamin Wu ◽  
David Thomas ◽  
...  
Keyword(s):  
Oral Dose ◽  
Oral Administration ◽  
Antimalarial Drug ◽  
Dose Range ◽  
Plasmodium Species ◽  
Repeat Dose ◽  
Nonlinear Kinetics ◽  
Dose Administration ◽  
Blood Concentrations ◽  
Cynomolgus Macaques

The purpose of this study was to evaluate the bioavailability and pharmacokinetics of a new antimalarial drug, AQ-13, a structural analog of chloroquine (CQ) that is active against CQ-resistant Plasmodium species, in rats and cynomolgus macaques. Sprague-Dawley rats ( n = 4 /sex) were administered a single dose of AQ-13 intravenously (i.v.) (10 mg/kg) or orally (20 or 102 mg/kg). Blood and plasma samples were collected at several timepoints. AQ-13 achieved Cmax after oral administration at approximately 3 to 4 h and could be detected in blood for 2 to 5 days after oral administration. The ratio of area under the curve (AUC) values at the high and low dose for AQ-13 deviated from an expected ratio of 5.0, indicating nonlinear kinetics. A metabolite peak was noted in the chromatograms that was identified as monodesethyl AQ-13. Oral bioavailability of AQ-13 was good, approximately 70%. The pharmacokinetics of AQ-13 was also determined in cynomolgus macaques after single (i.v., 10 mg/kg; oral, 20 or 100 mg/kg) and multiple doses (oral loading dose of 50, 100, or 200 mg/kg on first day followed by oral maintenance dose of 25, 50, or 100 mg/kg, respectively, for 6 days). The AUC and Cmax values following single oral dose administration were not dose proportional; the Cmax value for AQ-13 was 15-fold higher following an oral dose of 100 mg/kg compared to 20 mg/kg. MonodesethylAQ-13 was a significant metabolite formed by cynomolgus macaques and the corresponding Cmax values for this metabolite increased only 3.8-fold over the dose range, suggesting that the formation of monodesethyl AQ-13 is saturable in this species. The bioavailability of AQ-13 in cynomolgus macaques following oral administration was 23.8% for the 20-mg/kg group and 47.6% for the 100-mg/kg group. Following repeat dose administration, high concentrations of monodesethyl AQ-13 were observed in the blood by day 4, exceeding the AQ-13 blood concentrations through day 22. Saturation of metabolic pathways and reduced metabolite elimination after higher doses are suggested to play a key role in AQ-13 pharmacokinetics in macaques. In summary, the pharmacokinetic profile and metabolism ofAQ-13 are very similar to that reported in the literature for chloroquine, suggesting that this new agent is a promising candidate for further development for the treatment of chloroquine-resistant malaria.

scholarly journals Effect of taurine administration for muscle cramp in chronic liver disease. A case of decompensated liver cirrhosis in which muscle cramp disappeared after oral administration of taurine.

Kanzo ◽  
1990 ◽  
Vol 31 (12) ◽  
pp. 1464-1469 ◽  
Author(s):  
Yasushi MATSUZAKI ◽  
Naomi TANAKA ◽  
Takashi YAMAGUCHI ◽  
Yoshimichi CHUGANJI ◽  
Masaaki NISHI ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Liver Disease ◽  
Oral Administration ◽  
Chronic Liver Disease ◽  
Chronic Liver ◽  
Muscle Cramp ◽  
Decompensated Liver Cirrhosis

scholarly journals Asthenia and fatigue in hyperammonemia: etiopathogenesis and methods of correction

2022 ◽  
pp. 95-104
Author(s):  
E. Yu. Plotnikova ◽  
M. N. Sinkova ◽  
L. K. Isakov
Keyword(s):  
Liver Disease ◽  
Liver Diseases ◽  
Signs And Symptoms ◽  
Chronic Liver ◽  
Blood Levels ◽  
Chronic Liver Diseases ◽  
Life Threatening ◽  
Underlying Causes ◽  
Principles Of Treatment ◽  
The Brain

Asthenia and fatigue are the most common syndromes in patients with liver disease, which significantly affects their quality of life. The prevalence of fatigue in chronic liver diseases is from 50% to 85%. While some progress has been made in understanding the processes that can cause fatigue in general, the underlying causes of fatigue associated with liver disease remain not well understood. In particular, many data suggest that fatigue associated with liver disease likely results from changes in neurotransmission in the brain against the background of hyperammonemia. Hyperammonemia is a metabolic state characterized by an increased level of  ammonia, a  nitrogen-containing compound. The  present review describes hyperammonemia, which is likely important in the pathogenesis of fatigue associated with liver disease. Ammonia is a potent neurotoxin, its elevated blood levels can cause neurological signs and symptoms that can be acute or chronic, depending on the  underlying pathology. Hyperammonemia should be recognized early, and immediately treated to prevent the development of life-threatening complications, such as, swelling of the brain and coma. The article gives pathophysiological mechanisms of influence of hyperammonemia on state of psychovegetative status of patients with liver diseases, also lists basic principles of treatment. A significant part of the article is devoted to L-ornithine-L-aspartate, which is effective in asthenia and fatigue to reduce the level of hyperammonemia through a variety of well-studied mechanisms in chronic liver diseases.

Acetonitrile Serum Concentrations and Cyanide Blood Levels in a Case of Suicidal Oral Acetonitrile Ingestion

1991 ◽  
Vol 29 (4) ◽  
pp. 447-458 ◽  
Author(s):  
Hans Christoph Michaelis ◽  
Christian Clemens ◽  
Harald Kijewski ◽  
Hartmud Neurath ◽  
Angelika Eggert
Keyword(s):  
Blood Levels ◽  
Serum Concentrations
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