scholarly journals Erythropoietin kinetics in rats: generation and clearance

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 646-649
Author(s):  
SE Steinberg ◽  
JF Garcia ◽  
GR Matzke ◽  
J Mladenovic
Keyword(s):  
Intravenous Injection ◽  
Plasma Volume ◽  
Rat Model ◽  
Clearance Rate ◽  
Half Life ◽  
Plasma Clearance ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Two Compartment Model ◽  
Disappearance Curve

Detailed studies to analyze the early events of erythropoietin (Ep) secretion and clearance were performed in a rat model using a double antibody radioimmunoassay. Ep clearance was determined following intravenous injection of 1 mL of Ep-rich plasma, 1,080 mU/mL, obtained from phlebotomized rats. Analysis revealed a disappearance curve that conformed to a two-compartment model with an alpha half-life t1/2 of 3.6 minutes and a beta t1/2 of 86 minutes. The volume of distribution was similar to the calculated plasma volume. In anephric animals, there was no change in the plasma clearance rate or the volume of distribution. Rapid Ep secretion was elicited by a single 15 mL/kg phlebotomy (hematocrit decrement 45% to 30%), so that levels reached 20 to 30 times baseline (524 +/- 76 v 24 +/- 7 mU/mL) at five hours, whereas they plateaued for at least 33 hours. The increase in the rate of secretion was geometric, from 9.9 mU/h baseline secretion to 429 mU/h. These data identify a very sensitive and rapidly responsive system for Ep modulation in the rat.

scholarly journals Erythropoietin kinetics in rats: generation and clearance

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 646-649 ◽  
Author(s):  
SE Steinberg ◽  
JF Garcia ◽  
GR Matzke ◽  
J Mladenovic
Keyword(s):  
Intravenous Injection ◽  
Plasma Volume ◽  
Rat Model ◽  
Clearance Rate ◽  
Half Life ◽  
Plasma Clearance ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Two Compartment Model ◽  
Disappearance Curve

Abstract Detailed studies to analyze the early events of erythropoietin (Ep) secretion and clearance were performed in a rat model using a double antibody radioimmunoassay. Ep clearance was determined following intravenous injection of 1 mL of Ep-rich plasma, 1,080 mU/mL, obtained from phlebotomized rats. Analysis revealed a disappearance curve that conformed to a two-compartment model with an alpha half-life t1/2 of 3.6 minutes and a beta t1/2 of 86 minutes. The volume of distribution was similar to the calculated plasma volume. In anephric animals, there was no change in the plasma clearance rate or the volume of distribution. Rapid Ep secretion was elicited by a single 15 mL/kg phlebotomy (hematocrit decrement 45% to 30%), so that levels reached 20 to 30 times baseline (524 +/- 76 v 24 +/- 7 mU/mL) at five hours, whereas they plateaued for at least 33 hours. The increase in the rate of secretion was geometric, from 9.9 mU/h baseline secretion to 429 mU/h. These data identify a very sensitive and rapidly responsive system for Ep modulation in the rat.

Disappearance of palmitic acid from plasma of fetal and newborn sheep

1993 ◽  
Vol 74 (1) ◽  
pp. 62-67 ◽  
Author(s):  
G. G. Power ◽  
Y. Yoneyama ◽  
H. Asakura ◽  
R. Sawa
Keyword(s):  
Palmitic Acid ◽  
Clearance Rate ◽  
Half Life ◽  
Plasma Clearance ◽  
Exponential Model ◽  
Volume Of Distribution ◽  
Membrane Transporter ◽  
Double Exponential ◽  
Disappearance Curve ◽  
Double Exponential Model

These studies were undertaken to measure the kinetic constants that characterize the disappearance of a representative free fatty acid (FFA) from the plasma of fetal and newborn sheep. A bolus of albumin-complexed [14C]palmitic acid was infused intravenously, and during the next 8 min, 24 arterial samples were collected to characterize the disappearance curve. Palmitic acid disappearance from plasma was well described by a double-exponential model. When birth was simulated in utero, kinetic values were not changed by cooling. However, after intrauterine ventilation with O2, the volume of distribution of the FFA increased 29%, its plasma clearance rate decreased 26%, and its apparent half-life in the plasma lengthened from 0.8 to 1.2 min (all P < 0.01, n = 8). After umbilical cord occlusion, plasma clearance rate decreased a further 19% and half-life lengthened to 1.4 min. About 60% of the increase in FFA concentration during simulated birth is explained by increased release from adipose stores, and 40% is explained by decreased clearance. Further experiments tested the influence of FFA concentrations themselves. After infusion of unlabeled FFA, clearance of the tracer decreased 23% (P < 0.05, n = 5), a result consistent with a saturable membrane transporter of FFAs.

DYNAMICS OF PROGESTERONE METABOLISM IN THE PSEUDOPREGNANT RAT

1981 ◽  
Vol 90 (3) ◽  
pp. 359-366 ◽  
Author(s):  
J. ROBINSON ◽  
B. J. MERRY ◽  
M. E. LIGHTFOOT ◽  
A. K. HALL
Keyword(s):  
Plasma Volume ◽  
Clearance Rate ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Two Compartment Model ◽  
Progesterone Metabolism ◽  
Animal Preparation ◽  
Reductive Metabolism

The characteristics of the disappearance of progesterone and 20α-dihydroprogesterone from blood were examined in rats made pseudopregnant by administration of gonadotrophins. Measurement of the disappearance of [3H]progesterone from blood indicated that progesterone metabolism can be represented by a two-compartment model in this animal preparation. The disappearance of [3H]progesterone from blood was described by two half-lives of 0·5 and 11·7 min. The metabolic clearance rate for this steroid was 2·9 litre/day, equivalent to a production rate of 3·9 μmol/day. The initial volume of distribution of the injected [3H]progesterone was 5·0 ml, a volume similar in size to the expected plasma volume. The total volume of distribution of [3H]progesterone (i.e. 'inner' and 'outer' pools) was in the range 24·8–35·4 ml. The disappearance of endogenous progesterone from the blood of pseudopregnant rats after vascular isolation of the ovaries showed two half-lives of 1·1 and 11·4 min respectively. The disappearance of a product of reductive metabolism of progesterone, 20α-dihydroprogesterone, was apparently uniphasic, with a half-life of 41·3 min.

Pharmacokinetic studies on Sulfamonomethoxine in rabbits

2019 ◽  
Vol 20 (2) ◽  
pp. 92-97
Author(s):  
M Amer ◽  
M Elsayed ◽  
S Kazawaki ◽  
W Fathy ◽  
Eman El-Ashry
Keyword(s):  
Half Life ◽  
Area Under The Curve ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
The Body ◽  
Pharmacokinetic Studies ◽  
Plasma Drug ◽  
Time Data ◽  
Drug Concentrations ◽  
Two Compartment Model

The present study was performed to determine the pharmacokinetics of sulfamonomethoxine (20mg/kg) in 5 rabbits after its oral and intravenous administration. Blood samples were collected immediately before (time 0) and at 0.08, 0.25, 0.5, 1, 3, 5 and 8 hours post-dosing to evaluate the pharmacokinetics of sulfamonomethoxine. Plasma sulfamonomethoxine concentrations were quantified with HPLC-UV, and plasma drug concentration versus time data after IV was best fitted to the two-compartment model, characterized with the distribution phase (α) equaled to 2.05 h-1 with a distribution half-life [t0.5(α)] equaled to 0.61 h. The volume of distribution of (V1c) was 0.15 ml/kg., whereas the volume of distribution at a steady – state [Vdss] was 0.20 ml/kg, and the body clearance was 0.03 ml/ kg / h. After oral administration of SMM, plasma drug concentrations were best fitted to a two-compartment model, of which the mean half-life of absorption (t1/2ab) and elimination (t1/2β) were 0.02 and 1.99 h, respectively. The maximal absorption concentration (Cmax) was estimated as 114.06 µg/ml at 0.12 h, and the Area under the curve (AUC) was 340.42 µg/ml/h.

scholarly journals Pharmacokinetics and Efficacy of Piperaquine and Chloroquine in Melanesian Children with Uncomplicated Malaria

2007 ◽  
Vol 52 (1) ◽  
pp. 237-243 ◽  
Author(s):  
Harin A. Karunajeewa ◽  
Kenneth F. Ilett ◽  
Ivo Mueller ◽  
Peter Siba ◽  
Irwin Law ◽  
...  
Keyword(s):  
Half Life ◽  
Uncomplicated Malaria ◽  
Active Metabolite ◽  
High Performance ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Two Compartment Model ◽  
Elimination Half ◽  
Median Volume ◽  
Intensive Sampling

ABSTRACT The disposition of chloroquine (CQ) and the related 4-aminoquinoline, piperaquine (PQ), were compared in Papua New Guinean children with uncomplicated malaria. Twenty-two children were randomized to 3 days of PQ phosphate at 20 mg/kg/day (12 mg of PQ base/kg/day) coformulated with dihydroartemisinin (DHA-PQ), and twenty children were randomized to 3 days of CQ at 10 mg base/kg/day with a single dose of sulfadoxine-pyrimethamine (CQ-SP). After a 42-day intensive sampling protocol, PQ, CQ, and its active metabolite monodesethyl-chloroquine (DECQ) were assayed in plasma by using high-performance liquid chromatography. A two-compartment model with first-order absorption was fitted to the PQ and CQ data. There were no significant differences in age, gender, body weight, or admission parasitemia between the two groups. The PCR-corrected 42-day adequate clinical and parasitological responses were 100% for DHA-PQ and 94% for CQ-SP, but P. falciparum reinfections during follow-up were common (33 and 18%, respectively). For PQ, the median volume of distribution at steady state, allowing for bioavailability (V ss/F), was 431 liters/kg (interquartile range [IQR], 283 to 588 liters/kg), the median clearance (CL/F) was 0.85 liters/h/kg (IQR, 0.67 to 1.06 liters/h/kg), the median distribution half-life (t 1/2 α) was 0.12 h (IQR, 0.05 to 0.66 h), and the median elimination half-life (t 1/2 β) was 413 h (IQR, 318 to 516 h). For CQ, the median V ss/F was 154 liters/kg (IQR, 101 to 210 liters/kg), the median CL/F was 0.80 liters/h/kg (IQR, 0.52 to 0.96 liters/h/kg), the median t 1/2 α was 0.43 h (IQR, 0.05 to 1.82 h), and the median t 1/2 β was 233 h (IQR, 206 to 298 h). The noncompartmentally derived median DECQ t 1/2 β was 290 h (IQR, 236 to 368 h). Combined molar concentrations of DECQ and CQ were higher than those of PQ during the elimination phase. Although PQ has a longer t 1/2 β than CQ, its prompt distribution and lack of active metabolite may limit its posttreatment malaria-suppressive properties.

Pulmonary transvascular flux of transferrin

1989 ◽  
Vol 67 (5) ◽  
pp. 1850-1854 ◽  
Author(s):  
J. A. Cooper ◽  
A. B. Malik
Keyword(s):  
Plasma Concentration ◽  
Clearance Rate ◽  
Compartment Model ◽  
Input Function ◽  
Volume Of Distribution ◽  
Blood Pool ◽  
Two Compartment Model ◽  
Clearance Rate Constant ◽  
Extravascular Volume ◽  
Lung Lymph

We compared the pulmonary transvascular fluxes of transferrin and albumin in the intact sheep lung. Anesthetized sheep were prepared with lung lymph fistulas. The vascular blood pool was marked with 99mTc-erythrocytes, autologous transferrin was labeled with 113mIn, and albumin was labeled with 125I. Samples of blood, plasma, lymph, and lung were obtained up to 180 min after tracer infusion. Lymph tissue radioactivities were corrected for the intravascular component and expressed as extravascular-to-plasma concentration ratios. Clearance of transferrin and albumin from the plasma space followed a two-compartment model. The clearance rate constant was 2.1 +/- 0.1 x 10(-3) min for albumin and 2.4 +/- 0.1 x 10(-3) min for transferrin (P less than 0.05). Lymph-to-plasma ratios for albumin and transferrin were not different. However, the extravascular-to-plasma ratio for albumin was greater than transferrin (P less than 0.05). The lymph and lung data were deconvoluted for the plasma input function and fit to a two-compartment model. The results indicate that albumin and transferrin have similar permeabilities across the vascular barrier but have different pulmonary circulation to lymph kinetics because the extravascular volume of distribution of albumin is greater than transferrin.

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 Tissue Residues of Sulfathiazole and Sulfamethazine in Pigs

1994 ◽  
Vol 57 (9) ◽  
pp. 796-801 ◽  
Author(s):  
LIEVE S. G. VAN POUCKE ◽  
CARLOS H. VAN PETEGHEM
Keyword(s):  
Intravenous Injection ◽  
Half Life ◽  
Intramuscular Injection ◽  
Compartment Model ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Tissue Concentrations ◽  
Single Intravenous Injection ◽  
The Individual ◽  
Residue Study

The plasma pharmacokinetics and tissue penetration of sulfathiazole (ST) and sulfamethazine (SM) after intravenous and intramuscular injection in pigs were studied. Following a single intravenous dose of 40 mg ST/kg of bodyweight or 80 mg SM/kg of bodyweight, the plasma ST and SM concentrations were best fitted to a two-compartment model. The areas under the curve were 447 ± 39 and 1485 ± 41 mg/h/L, clearances were 0.090 ± 0.007 and 0.054 ± 0.001 L/kg/h, volumes of distribution were 1.16 ± 0.16 and 0.77 ± 0.06 L/kg, half-lifes in distribution phase were l.18 ± 0.57 and 0.23 ± 0.16 h and half-lifes in eliminations phase were 9.0 ± l.6 and 9.8 ± 0.6 h. When the two compounds were administered simultaneously as a single intravenous injection, the pharmacokinetic parameters for ST were not significantly different. The values for SM show statistical differences for some important parameters: α, β and the AUC0–&gt;∞ were significantly decreased and t1/2α, Vd and CIB were significantly increased. It can be concluded that after a single intravenous injection of 40 mg/kg, sulfathiazole has a high tl/2β resulting in higher tissue concentrations. This half-life, which is higher than what is reported in the literature, is not influenced by the simultaneous presence of sulfamethazine. The tl/2β for sulfamethazine after a single intravenous injection of 80 mg/kg is comparable to the data from the literature and is not influenced by the presence of sulfathiazole. Sulfathiazole and SM were also administered simultaneously as an intramuscular injection to healthy pigs at a dosage of 40 and 80 mg/kg bodyweight. Pharmacokinetic experiments were conducted on three pigs. From this pharmacokinetic study it can be concluded that upon a single intramuscular administration of 40 mg/kg of ST and 80 mg/kg of SM the absolute bioavailability in pigs is 0.92 ± 0.04 for ST and l.01 ± 0.07 for SM. Six pigs received five intramuscular im) injections as a single dose of ST and SM every 24 h for five consecutive days for the residue study. The pigs were slaughtered at different times after the last dose was given and samples were taken from various tissues and organs. Concentrations were determined by a microbiological method and a HPTLC method. No edible tissue contained more than 100 μg/kg of the individual sulfonamides after 10 days of withdrawal. It means that adult animals which have a shorter half-life and thus lower tissue concentrations will certainly meet the economic community EC) maximum residue limits after a 10 days withdrawal period.

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