Distribution and kinetics of amylin in humans

1998 ◽  
Vol 274 (5) ◽  
pp. E903-E908 ◽  
Author(s):  
M. Clodi ◽  
K. Thomaseth ◽  
G. Pacini ◽  
K. Hermann ◽  
A. Kautzky-Willer ◽  
...  
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
C Peptide ◽  
Fractional Clearance ◽  
Cell Hormone ◽  
Total Body ◽  
Relationship Of ◽  
Kinetics Of ◽  
Male Subjects ◽  
Apparent Volume Of Distribution

The aim of the study was to determine the apparent volume of distribution (VTOT), total body clearance (CL), fractional clearance, and mean residence time (MRT) of the β-cell hormone amylin. We therefore performed an intravenous injection of 50 μg of human synthetic amylin (amlintide) in nine healthy male subjects during suppression of endogenous amylin release by intravenous somatostatin (0.06 μg ⋅ kg−1⋅ min−1). The plasma levels of amylin concentrations over time were analyzed using three-exponential curves. VTOTwas 173 ± 16 ml/kg and was not different from that of insulin reported in the literature (157 ml/kg). MRT was 27.7 ± 2.1 min and thus two times the reported value for insulin (14.1 min) and C-peptide (16.4 min). CL and fractional CL were 6.2 ± 0.2 ml ⋅ kg−1⋅ min−1and 0.038 ± 0.003 min−1, respectively. Fractional CL is therefore definitely lower than that reported for insulin (0.12–0.2 min−1) but is, however, in the range of that of C-peptide (0.05 min−1). In conclusion, clearance of amylin is similar to that reported for C-peptide and much slower than insulin, indicating that the commonly used molar insulin-to-amylin ratio does not reflect the correct relationship of the two peptides.

Inhibitory effect of phenelzine on oxidative microsomal enzyme systems of rat liver

1983 ◽  
Vol 61 (5) ◽  
pp. 524-529 ◽  
Author(s):  
P. M. Bélanger ◽  
A. Atitsé-Gbeassor
Keyword(s):  
Rat Liver ◽  
Apparent Volume ◽  
Inhibitory Effect ◽  
Volume Of Distribution ◽  
Inhibitory Effects ◽  
Oxidative Reactions ◽  
Total Body ◽  
Apparent Volume Of Distribution ◽  
Cytochrome P 450 ◽  
Substrate Addition

The inhibitory effects of phenelzine on the hepatic microsomal demethylation of aminopyrine, N,N-dimethylaniline, and p-nitroanisole on the hydroxylation of aniline and on the pharmacokinetics of antipyrine were investigated in the rat. Phenelzine produced a competitive and noncompetitive inhibition of the demethylation of p-nitroanisole and N,N-dimethylaniline, respectively, but was a mixed-type inhibitor of the aminopyrine N-demethylase and aniline hydroxylase. The inhibition constant, Ki, varied between 0.06 to 0.25 mM depending on the substrate used. Preincubation of phenelzine for 30 min with the microsomal homogenate prior to substrate addition doubled its inhibitory effect. Phenelzine induced a type II spectral change when combined with oxidized cytochrome P-450 with a Ks value of 0.4 mM. The administration of one dose of 50 mg∙kg−1 of phenelzine sulfate concomitantly with 50 mg∙kg−1 of antipyrine resulted in a significant decrease of the serum elimination of antipyrine. The serum half-life, apparent volume of distribution, and total body clearance of antipyrine were modified to 3.6 h, 294.1 mL∙kg−1, and 56.8 mL∙h−1∙kg−1, respectively, from 1.5 h, 666.7 mL∙kg−1, and 312.5 mL∙h−1∙kg−1 when antipyrine was administered alone. It is concluded that the inhibitory effect of phenelzine on the microsomal oxidative reactions of rat liver is related to its interaction with cytochrome P-450.

scholarly journals Disposition Kinetics of Amitraz in Lactating Does

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4769
Author(s):  
Sathish Nanjundappa ◽  
Suresh Narayanan Nair ◽  
Darsana Udayan ◽  
Sreelekha Kanapadinchareveetil ◽  
Mathew Jacob ◽  
...  
Keyword(s):  
High Performance ◽  
Area Under The Curve ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Health Concern ◽  
Laboratory Animals ◽  
Disposition Kinetics ◽  
Kinetics Of ◽  
Apparent Volume Of Distribution ◽  
Dermal Application

Amitraz, a member of the formamidine pesticide family, commonly used for ectoparasite control, is applied as a dip or low-pressure hand spray to cattle and swine, and the neck collar on dogs. Data on amitraz were generated mainly on laboratory animals, hens, dogs, and baboons. The data on the toxicity and disposition of amitraz in animals and its residues in the milk are inadequate. Therefore, the present study was intended to analyze the disposition kinetics of amitraz and its pattern of elimination in the milk of lactating does after a single dermal application at a concentration of 0.25%. Blood at predetermined time intervals and milk twice daily were collected for eight days post application. The drug concentration was assayed by high-performance liquid chromatography (HPLC). Amitraz was detected in whole blood as early as 0.5 h, which attained a peak concentration at 12 ± 5 h, followed by a steady decline; however, detection persisted until 168 h. Amitraz was present in the blood at its 50% Cmax even after 48 h, and was still detectable after 7 days. The disposition after a single dermal application was best described non-compartmentally. The mean terminal half-life (t1/2), mean residence time (MRT), and area under the curve (AUC0–t) were 111 ± 31 h, 168 ± 39 h, and 539 ± 211 µg/mL/h, respectively. The apparent volume of distribution (Vdarea) was 92 ± 36 mL/g with an observed clearance (Cl) of 0.57 ± 0.33 mL/kg/h. Thus, the drug was well absorbed, widely distributed and slowly eliminated from the animal body. Amitraz achieved milk concentration approximating 0.2 per cent of the total dose after a single exposure and the steady-state elimination of amitraz in milk above the recommended maximum residue limit (MRL) of 0.01 mg/kg can act as a source of public health concern when applied on lactating animals.

Individualization of Theophylline Dosage in Adults with Bronchial Asthma

1986 ◽  
Vol 20 (9) ◽  
pp. 704-707 ◽  
Author(s):  
Maria J. Otero ◽  
Miguel Barrueco ◽  
Eduardo L. Marino ◽  
Francisco Gomez ◽  
Alfonso Dominguez-Gil
Keyword(s):  
Elderly Patients ◽  
Bronchial Asthma ◽  
Total Body Clearance ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Dosage Regimens ◽  
Elimination Half ◽  
Total Body ◽  
Apparent Volume Of Distribution ◽  
Body Clearance

The influence of age on the disposition of theophylline was studied in 95 adult patients (nonsmokers) with bronchial asthma requiring oral theophylline therapy: 17 patients age ≥39 years, 50 patients age 40–59 years, and 28 patients < 60 years. A decrease was observed in total body clearance together with an increase in the elimination half-life of theophylline parallel to the advance in age of the patients. The apparent volume of distribution of theophylline was similar in the three groups of patients. According to the results obtained, recommendations are made regarding the dosage regimens of theophylline in elderly patients.

Chloramphenicol Pharmacokinetics in Infants and Young Children

PEDIATRICS ◽  
1980 ◽  
Vol 66 (4) ◽  
pp. 579-584
Author(s):  
Carolyn M. Sack ◽  
Jeffrey R. Koup ◽  
Arnold L. Smith
Keyword(s):  
Pediatric Patients ◽  
Total Body Clearance ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Wide Variability ◽  
Chloramphenicol Succinate ◽  
Total Body ◽  
Apparent Volume Of Distribution ◽  
Infants And Young Children ◽  
Body Clearance

We measured serum chloramphenicol concentrations in 17 hospitalized pediatric patients (aged 1 month to 6 years) after intravenous infusion of chloramphenicol succinate. The serum T½ ranged from 2.1 to 8.3 hours with a mean of 3.98 (SD 1.75) hours, while the apparent volume of distribution ranged from 0.78 to 2.09 liters/kg with a mean of 1.39 (SD 0.34) liters/kg. The total body clearance ranged 0.122 to 0.429 liters/kg/hour with a mean of 0.281 (SD 0.117) liters/kg/hour. Two patients were restudied, and had increased clearance during their hospitalization. Because of the wide variability in pharmacokinetics, we conclude that serum chloramphenicol concentrations should be monitored in infants and children.

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.

Serum Quinidine Levels after Chronic Administration of Four Different Quinidine Formulations

1976 ◽  
Vol 4 (6) ◽  
pp. 393-401 ◽  
Author(s):  
A M Soeterboek ◽  
M Van Thiel
Keyword(s):  
Serum Level ◽  
Chronic Administration ◽  
Serum Levels ◽  
Relative Bioavailability ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Level Curves ◽  
Trough Serum ◽  
Total Body ◽  
Apparent Volume Of Distribution

The serum levels produced by four different quinidine formulations have been studied. The relative bioavailability of the formulations was demonstrated as were the mean peak serum levels and their timing in relation to dosage. From the data obtained, the biological half-lives were measured and the apparent volume of distribution and total body clearance were calculated for each formulation. The generic tablets of quinidine monosulphate from five different manufacturers were not significantly different from each other in any respect and produced the expected peak and trough serum level curves. The serum level curves resulting from administration of quinidine polygalacturonate (Cardioquin®) were not significantly different from those resulting from the generic tablets, and this formulation may be regarded as therapeutically equivalent to the generic formulations. Both sustained-release formulations of quinidine bisulphate, Durettes® and Kiditard® (given at the same dosage) were shown to offer a means whereby, with simple twice-daily dosage, quinidine maintenance treatment may be continued with the confidence that the serum levels may be maintained throughout each 24-hour period without peaks into the toxic levels and troughs into the levels of no effect.

scholarly journals Intravascular plasma disposition and salivary secretion of closantel and rafoxanide in sheep

1999 ◽  
Vol 70 (2) ◽  
Author(s):  
G.E. Swan ◽  
H.A. Koeleman ◽  
H.S. Steyn ◽  
M.S.G. Mülders
Keyword(s):  
Pharmacokinetic Profile ◽  
Apparent Volume ◽  
Salivary Secretion ◽  
Volume Of Distribution ◽  
Large Individual ◽  
Drug Plasma ◽  
Elimination Half ◽  
Proportional Increase ◽  
Total Body ◽  
Apparent Volume Of Distribution

The plasma and salivary disposition of closantel and rafoxanide were examined following intravenous administration in adult sheep. Two studies were conducted with rafoxanide at 7.5 mg/kg and 1 with closantel using 2 doses (5 and 15 mg/kg). The pharmacokinetic profile of both drugs in plasma were best described by a 2-compartmental model with 1st-order rate constants. Plasma disposition of closantel and rafoxanide were characterised by a rapid distribution (t1/2(a) of <30 min), long elimination half-life (t1/2(b) of 17.0 + 4.0 days for closantel and 7.2 + 0.6 days for rafoxanide), small apparent volume of distribution (Vss of <0.15 ℓ/kg) and a slow rate of total body clearance (Cl of <0.01mℓ/min/kg). The area under the drug plasma concentration curve (AUC) of closantel at 5 mg/kg was nearly twice as large as that of rafoxanide at 7.5 mg/kg resulting from the slower t1/2(b) observed with closantel compared to rafoxanide. Large individual differences were observed in the rate measurements of distribution (k12, k21 and t1/2(a)), whereas the parameters of elimination (k10, t1/2(b) and Cl), were more consistent between animals. A dose proportional increase in AUC was observed for closantel administered at 5 and 15 mg/kg. A low, constant salivary concentration of closantel (mean of 0.04+0.05 mg/mℓ) and rafoxanide (mean of 0.07+0.04 mg/mℓ) was observed during the 24-h examination period after dosing.

Toxicokinetics of Colchicine in Humans: Analysis of Tissue, Plasma and Urine Data in Ten Cases

1992 ◽  
Vol 11 (6) ◽  
pp. 510-516 ◽  
Author(s):  
M. Rochdi ◽  
A. Sabouraud ◽  
F.J. Baud ◽  
C. Bismuth ◽  
J.M. Scherrmann
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Analysis ◽  
Post Mortem ◽  
Elimination Half ◽  
High Concentrations ◽  
Human Poisoning ◽  
Total Body ◽  
Therapeutic Doses ◽  
Kinetics Of

1 A specific and sensitive radioimmunoassay was used to study the toxicokinetics of colchicine in seven cases of acute human poisoning. Post-mortem tissue concentrations of colchicine were measured in three further cases. Depending on the time of patient admission, two disposition processes could be observed. The first, in three patients, admitted early, showed a bi-exponential plasma colchicine decrease, with distribution half-lives of 30, 45 and 90 min. The second, in four patients, admitted late, showed a mono-exponential decrease. Plasma terminal half-lives ranged from 10.6 to 31.7 h for both groups. 2 Pharmacokinetic analysis of urine colchicine data was performed for two patients. The fraction of unchanged colchicine excreted in urine was about 30%, renal clearance was about 131 h-1 and three-fold less than total body clearance (391 h-1). The apparent volume of distribution was 211 kg-1. 3 Post-mortem tissue analysis showed an ubiquitous colchicine distribution. Colchicine accumulated at high concentrations in the bone marrow (more than 600 ng g-1), testicle (400 ng g-1), spleen (250 ng g-1), kidney (200 ng g-1), lung (200 ng g-1) and heart (95 ng g -1); it was also found in the brain (125 ng g-1). 4 This toxicokinetic study shows that after massive ingestion, the disposition parameters and kinetics of colchicine are not markedly modified from those occuring in healthy volunteers. The absorption process was not delayed and the distribution and elimination half-lives were in the range known to occur with therapeutic doses.

Pharmacokinetics and Tissue Distribution of Norfloxacin in Eel Following Oral Gavage

2012 ◽  
Vol 452-453 ◽  
pp. 1069-1073
Author(s):  
Yun Hua Hui ◽  
You Qiong Cai ◽  
Bing Feng ◽  
Wen Ruan ◽  
Hui Juan Yu
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
European Eel ◽  
Half Time ◽  
Oral Gavage ◽  
Concentration Time ◽  
Liver And Kidney ◽  
Apparent Volume Of Distribution ◽  
Different Tissues ◽  
Body Clearance

The pharmacokinetics of norfloxacin were investigated in the European eel after a single oral gavage of 10 mg norfloxacin per kg body weight. The concentrations of norfloxacin in the main tissues (kidney, muscle, hepatopancreas and blood) were simultaneously detected by HPLC. All of the concentration-time curves of norfloxacin in the plasma, muscle and liver were consistent with absorption of a two-compartment open kinetic model. Norfloxacin was widely distributed in different tissues in the European eel. Apparent volume of distribution (Vd) was 52.025 L/kg, 34.589 L/kg, 2.795 L/kg, and 0.969 L/kg, in plasma, muscle, liver and kidney, respectively. Norfloxacin in the eel was proved to eliminate slowly, and half-time (tβ1/2) in plasma, muscle, liver and kidney, was 201.222 h, 123.789 h, 120.634 h and 627473.495 h, respectively. Body clearance was 0.689 L / ( kg•h ), 1.793 L/( kg•h ), 0.097 L/( kg•h ) and 0.028 L /( kg•h ), in plasma, muscle, liver and kidney, respectively.

Ketamine kinetics: decerebrate vs. intact cats

1979 ◽  
Vol 57 (8) ◽  
pp. 878-881 ◽  
Author(s):  
James E. Heavner ◽  
Duane C. Bloedow
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
Drug Dose ◽  
The Body ◽  
Pharmacokinetic Parameters ◽  
Peripheral Compartment ◽  
Blood Concentrations ◽  
Open Model ◽  
Apparent Volume Of Distribution ◽  
Compartment Open Model

Pharmacokinetic parameters of a ketamine (10 mg/kg, iv) bolus in decerebrate and intact cats were compared. A two-compartment open model best described the data in both groups. The apparent volume of distribution of the peripheral compartment, the apparent volume of distribution of the drug in the body, and the half-life of the postdistributive phase were significantly less (p < 0.05) in the decerebrate animals. These results emphasize the importance of correlating behavior and neuronal activity with plasma or blood concentrations of drug in animals rather than assuming that, for a given drug dose, blood (and thus tissue) levels of the agent will be similar regardless of how the animal is prepared for study.

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