scholarly journals Pharmacokinetics of ciprofloxacin in layer chicks

1999 ◽  
Vol 23 (1) ◽  
pp. 124-133
Author(s):  
B. S. AI – Khafaji ◽  
A. A. Al-Khayyat ◽  
O.M.S. Al-Shaha
Keyword(s):  
Plasma Level ◽  
Peak Plasma ◽  
Volume Of Distribution ◽  
Order Kinetic ◽  
Peak Plasma Level ◽  
Elimination Phase ◽  
First Order ◽  
Distribution Phase ◽  
Phase Phase ◽  
Biphasic Kinetic

Pharmacokinetics parameters of ciprofloxacin were calculated from constructed plasma disappearing curves (PDC) after oral or i.v. injection of 5mg / kg in two-week old hybird layer · The i.v. PDC indicated a first order biphasic kinetic. The distribution phase was too short to be considered. The parameters of the elimination phase phase indicated that the biological half – life ( t 12) was 3.7 hours and the volume of distribution (Vd) was 1.7 1/kg.  The oral PDC indicated a first order kinetic with a peak plasma level (PPL) of 3.0 ug/ml achieved after 1.75 hours , a t 12 of 2.9 hours and a Vd of 1.7 1/kg . Bioavailability value was 84 +9.7% . Binding of ciprofloxacin to chicken plasma protein was estimated to be 25.4 61.3%.

scholarly journals Pharmacokinetics of sodium meclofenamate in pre-ruminant cattle

2004 ◽  
Vol 56 (6) ◽  
pp. 695-700
Author(s):  
E.J. Picco ◽  
D.C. Diaz David ◽  
T. Encinas ◽  
M.R. Rubio ◽  
J.C. Boggio
Keyword(s):  
High Performance ◽  
Pharmacokinetic Profile ◽  
Apparent Volume ◽  
Antiinflammatory Drug ◽  
Volume Of Distribution ◽  
Intramuscular Administration ◽  
Flip Flop ◽  
Elimination Phase ◽  
Distribution Phase ◽  
Apparent Volume Of Distribution

The pharmacokinetic profile of sodium meclofenamate, a non-steroidal antiinflammatory drug, was determined in six pre-ruminant calves after intravenous and intramuscular administration at a dose of 2.2mg/kg of body weight. Meclofenamate concentrations were measured using a high performance liquid chromatography assay. The pharmacokinetics of sodium meclofenamate after intravenous and intramuscular administration to calves were characterised by a rapid distribution phase (t½alpha ), 15.45± 4.85min and 23.14± 7.24min for the intravenous and intramuscular administration, respectively, followed by a longer elimination phase (t½beta ) after intramuscular treatment (17.55± 6.52h.). The apparent volume of distribution (Vd) of the drug after intravenous administration was moderate (0.72± 0.12l/kg), and high (3.51± 1.05l/kg) after intramuscular administration. This can be explained by the flip-flop effect or by enterohepatic shunting. The bioavailability achieved after intramuscular administration was 61%.

scholarly journals The in vivo metabolism of recombinant human erythropoietin in the rat

Blood ◽  
1989 ◽  
Vol 73 (1) ◽  
pp. 90-99 ◽  
Author(s):  
JL Spivak ◽  
BB Hogans
Keyword(s):  
Recombinant Human Erythropoietin ◽  
Plasma Clearance ◽  
Dextran Sulfate ◽  
Volume Of Distribution ◽  
Human Albumin ◽  
Recombinant Erythropoietin ◽  
Elimination Phase ◽  
Human Erythropoietin ◽  
Distribution Phase

Abstract We compared the in vivo plasma clearance and organ accumulation in anesthetized rats of 125I-labeled, recombinant human erythropoietin and 125I-labeled, desialylated recombinant erythropoietin. The immediate volume of distribution of 125I-labeled, recombinant erythropoietin approximated that of the plasma volume. Its plasma clearance was multiexponential, with an initial rapid distribution phase (t1/2 = 53 minutes) and a slower elimination phase (t1/2 = 180 minutes). Organ accumulation of labeled recombinant erythropoietin, as compared with 125I-labeled human albumin, was negligible until 30 minutes after injection when small amounts appeared in the kidneys and bone marrow. Only 24% of the 125I-labeled, desialylated recombinant erythropoietin was recovered immediately after injection, and 96% of the hormone was cleared from the plasma with a t1/2 of 2.0 minutes. The bulk of the desialylated hormone accumulated in the liver where it was rapidly catabolized and its breakdown products released back into the plasma. Significantly, in contrast to unmodified erythropoietin, there was also early accumulation of desialylated hormone in the kidneys, marrow, and spleen. Desialylated orosomucoid but not orosomucoid, yeast mannan, or dextran sulfate 500 inhibited the rapid plasma clearance and hepatic accumulation of desialylated erythropoietin. Oxidation of the desialylated hormone restored its plasma recovery and clearance to normal but rendered it biologically inactive, and accumulation in organs other than the kidney was negligible.

scholarly journals The in vivo metabolism of recombinant human erythropoietin in the rat

Blood ◽  
1989 ◽  
Vol 73 (1) ◽  
pp. 90-99
Author(s):  
JL Spivak ◽  
BB Hogans
Keyword(s):  
Recombinant Human Erythropoietin ◽  
Plasma Clearance ◽  
Dextran Sulfate ◽  
Volume Of Distribution ◽  
Human Albumin ◽  
Recombinant Erythropoietin ◽  
Elimination Phase ◽  
Human Erythropoietin ◽  
Distribution Phase

We compared the in vivo plasma clearance and organ accumulation in anesthetized rats of 125I-labeled, recombinant human erythropoietin and 125I-labeled, desialylated recombinant erythropoietin. The immediate volume of distribution of 125I-labeled, recombinant erythropoietin approximated that of the plasma volume. Its plasma clearance was multiexponential, with an initial rapid distribution phase (t1/2 = 53 minutes) and a slower elimination phase (t1/2 = 180 minutes). Organ accumulation of labeled recombinant erythropoietin, as compared with 125I-labeled human albumin, was negligible until 30 minutes after injection when small amounts appeared in the kidneys and bone marrow. Only 24% of the 125I-labeled, desialylated recombinant erythropoietin was recovered immediately after injection, and 96% of the hormone was cleared from the plasma with a t1/2 of 2.0 minutes. The bulk of the desialylated hormone accumulated in the liver where it was rapidly catabolized and its breakdown products released back into the plasma. Significantly, in contrast to unmodified erythropoietin, there was also early accumulation of desialylated hormone in the kidneys, marrow, and spleen. Desialylated orosomucoid but not orosomucoid, yeast mannan, or dextran sulfate 500 inhibited the rapid plasma clearance and hepatic accumulation of desialylated erythropoietin. Oxidation of the desialylated hormone restored its plasma recovery and clearance to normal but rendered it biologically inactive, and accumulation in organs other than the kidney was negligible.

Pulmonary uptake of mannitol as an index of changes in lung epithelial permeability

1983 ◽  
Vol 55 (2) ◽  
pp. 614-618 ◽  
Author(s):  
S. M. Taylor ◽  
H. Downes ◽  
C. A. Hirshman ◽  
J. E. Peters ◽  
D. Leon
Keyword(s):  
Plasma Level ◽  
Peak Plasma ◽  
Human Studies ◽  
Antigen Challenge ◽  
Epithelial Permeability ◽  
Peak Plasma Level ◽  
Pulmonary Uptake ◽  
Lung Epithelial ◽  
Separate Control ◽  
Lung Epithelial Permeability

To develop a simple, inexpensive, and nontoxic test for changes in bronchial permeability we have employed a specific gas chromatographic assay to measure the uptake of mannitol from the lung after administration of an intratracheal aqueous bolus (8 ml of 5% solution). We have tested the ability of our method to detect the known increase in lung epithelial permeability elicited by challenge of previously sensitized animals with aerosols of Ascaris suum antigen. In Ascaris-sensitive Basenji-Greyhound dogs, antigen challenge significantly increased the rate of appearance and peak plasma level of mannitol after administration of the intratracheal bolus. Peak plasma mannitol levels averaged 25 +/- 3 (SE) micrograms/ml in dogs challenged with Ascaris antigen aerosols, and 14 +/- 2 micrograms/ml in the same animals in separate control experiments employing saline aerosols. The method presented could be readily applied to animal and human studies as a simple, inexpensive, and nontoxic indicator of lung epithelial permeability.

Oral Administration of Carbon-14 Labeled Cyanocobalamin (14C-Cbl) Reveals Variable Degradation of Vitamin B12 in the Gastrointestinal Tract That Impacts Vitamin B12 Absorption and Status.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3018-3018
Author(s):  
Ralph Green ◽  
Joshua W Miller ◽  
Kyung-Seon Lee ◽  
Syrukh Sutter ◽  
Lindsay H Allen ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Plasma Level ◽  
Oral Administration ◽  
Urinary Excretion ◽  
Vitamin B12 ◽  
Research Funding ◽  
Peak Plasma ◽  
Science Research ◽  
Fecal Excretion ◽  
Peak Plasma Level

Abstract Abstract 3018 Poster Board II-994 Recent evidence from our laboratory and others suggests that a variable portion of ingested cobalamin (Cbl), either crystalline or from food, is degraded in the gastrointestinal tract. We have developed a biosynthetic method to incorporate 14C into the lower axial ligand of cobalamin that has made it possible to study the fate of this vitamin during its passage through the gastrointestinal tract and to assess the presence of Cbl or its breakdown products in biological samples. Following oral administration of an aqueous physiological tracer dose of 14C-Cbl (1.3 μg, 50 nCi), blood, urine, and feces are analyzed for 14C by accelerator mass spectrometry. In 9 subjects, the plasma response was consistent with the expected behavior of peroral Cbl: 14C-Cbl first appeared in the plasma 3h post-dose reaching a peak level within 6-8h. Confirmation that this dose appears bound to the physiological transport protein transcobalamin (TC) was obtained in a subset of subjects by an immunoaffinity method using anti-human TC antibody-coated magnetic beads which selectively bound 95-98% of plasma 14C. Urinary excretion of 14C was maximal in the first 24h, with 14C first appearing in urine as early as 1.5h after dosing. Fecal excretion occurred variably over several days. The amount of 14C found in the urine (10-50% of the dose) was 100-fold greater than in previous reports using 57Co-labeled cyanocobalamin (0.1-0.5%), and fecal excretion was lower than expected (10-20% vs 30-70%). Urinary excretion of 14C was inversely correlated with the peak plasma level of 14C attained (r2=0.610; p<0.001). The bulk of urinary 14C was not associated with intact Cbl and first appeared in the urine before peak 14C levels were attained in the plasma. The peak plasma level of 14C attained also showed a strong positive correlation with plasma holotranscobalamin concentration measured before administration of the 14C-Cbl (r2=0.571; p<0.001). No such correlation was found with total plasma Cbl. In additional experiments on normal volunteers using eggs endogenously labeled with 14C Cbl following intramuscular injection of hens with 14C Cbl, comparably high urinary excretion of 14C was also observed. We conclude that a variable fraction of ingested Cbl is degraded in the gastrointestinal tract of normal individuals. This may be an important determinant of the amount of Cbl absorbed from food or supplement sources. Additionally, our findings suggest that the concentration of holoTC in the plasma reflects absorptive capacity and may therefore be a good surrogate for Cbl absorptive status. Our findings also have implications regarding the bioavailability of Cbl and may inform pending considerations to fortify food supplies with Cbl in order to mitigate the incidence of Cbl deficiency, particularly among the elderly. Intestinal degradation, either microbial or through the action of digestive enzymes, may also be a source of Cbl analogues that have previously been detected in the plasma and tissues. Cbl analogues may interfere with the physiological function of cobalamin, resulting in some of the manifestations of cobalamin deficiency. Disclosures: Green: Vitalea Science: Research Funding. Miller:Vitalea Science: Research Funding. Lee:Vitalea Science: Research Funding. Sutter:Vitalea Science: Research Funding. Allen:Vitalea Science: Research Funding. Dueker:Vitalea Science: Employment.

Toxicokinetics of Paraquat in Humans

1990 ◽  
Vol 9 (1) ◽  
pp. 5-12 ◽  
Author(s):  
P. Houzé ◽  
F.J. Baud ◽  
R. Mouy ◽  
C. Bismuth ◽  
R. Bourdon ◽  
...  
Keyword(s):  
Half Life ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Analysis ◽  
Elimination Phase ◽  
Specific Radioimmunoassay ◽  
Elimination Half ◽  
Distribution Phase ◽  
Human Poisoning ◽  
Apparent Volume Of Distribution

1 The toxicokinetics of paraquat were studied in 18 cases of acute human poisoning using a specific radioimmunoassay. Plasma paraquat concentration exhibited a mean distribution half-life ( t½ α) of 5 h and a mean elimination half-life ( t½ β) of 84 h. Cardiovascular collapse supervened early during the course of the intoxication and was associated with the distribution phase. Death related to pulmonary fibrosis occurred late and was associated with the elimination phase. 2 Pharmacokinetic analysis of urine paraquat excretion confirmed the biphasic decline of paraquat. Moreover, renal paraquat and creatinine clearances were not correlated but renal paraquat clearance was never higher than the renal creatinine clearance. 3 Tissue paraquat distribution was ubiquitous with an apparent volume of distribution ranging from 1.2 to 1.6 l/kg. Muscle could represent an important reservoir explaining the long persistence of paraquat in plasma and urine for several weeks or months after poisoning.

Self-Poisoning with the β-Blocker Bisoprolol

1990 ◽  
Vol 9 (4) ◽  
pp. 255-256 ◽  
Author(s):  
A. Tracqui ◽  
P. Kintz ◽  
P. Mangin ◽  
B. Lenoir
Keyword(s):  
Plasma Level ◽  
Peak Plasma ◽  
Sinus Bradycardia ◽  
Full Recovery ◽  
Peak Plasma Level ◽  
Β Blocker

A case of bisoprolol self-poisoning resulting in full recovery of the patient is described. The peak plasma level of bisoprolol was 541 ng ml-1. Sinus bradycardia was the only symptom observed, suggesting that cardioselectivity and absence of membrane stabilizing activity contribute to reduce the severity of β-blocker intoxication.

scholarly journals Disposition Kinetics and Dosage Regimen of Ceftriaxone in Crossbred Calves (Short Communication)

1999 ◽  
Vol 47 (2) ◽  
pp. 243-246 ◽  
Author(s):  
Bindu Johal ◽  
A. K. Srivastava
Keyword(s):  
Dosage Regimen ◽  
Peak Plasma ◽  
Binding Capacity ◽  
Volume Of Distribution ◽  
Dissociation Rate ◽  
Peak Plasma Level ◽  
Disposition Kinetics ◽  
Elimination Half ◽  
Total Body ◽  
Single Intravenous Administration

Disposition kinetics and urinary excretion of ceftriaxone were investigated in healthy crossbred calves after its single intravenous administration (10 mg kg–1). Based on kinetic parameters, an appropriate dosage regimen of ceftriaxone in calves was calculated. The peak plasma level of ceftriaxone at 1 min was 84.0 ± 1.55 μg ml–1 which declined to 0.43 ± 0.05 μg ml–1 at 8 h. The value of elimination half-life (t1/2α), volume of distribution Vd (area) and total body clearance (ClB) were 4.39 ± 0.63 h, 1.91 ± 0.19 L kg–1 and 0.31 ± 0.01 L kg–1 h–1, respectively. Approximately 41 per cent of total administered drug was recovered in the urine within 24 h of its administration. The plasma protein binding of ceftriaxone was found to be concentration dependent with an overall mean of 38.55 per cent. The binding capacity of ceftriaxone to plasma proteins and the dissociation rate constant of protein-drug complex were 20.1 × 10–8 ± 18.4 × 10–8 mole g–1 and 1.07 × 10–6 ± 0.52 × 10–6 mole, respectively. An appropriate intravenous dosage regimen of ceftriaxone in cattle would be 12 mg kg–1 repeated at 24 h.

scholarly journals Apixaban Interacts with Haemoglobin: Effects on Its Plasma Levels

2018 ◽  
Vol 118 (10) ◽  
pp. 1701-1712 ◽  
Author(s):  
Monica Sacco ◽  
Stefano Lancellotti ◽  
Federico Berruti ◽  
Alessandro Arcovito ◽  
Andrea Bellelli ◽  
...  
Keyword(s):  
Plasma Level ◽  
High Performance ◽  
Peak Plasma ◽  
Multivariable Analysis ◽  
Factor Xa ◽  
Reversed Phase ◽  
Peak Plasma Level ◽  
Red Cell Membrane ◽  
Docking Simulations ◽  
Oxygen Dissociation

AbstractThe direct oral anticoagulant apixaban (APX), a strong factor Xa inhibitor, binds also to plasma proteins, especially albumin, and minimally to α1-acid glycoprotein. Although APX can cross the red cell membrane, due to its chemical structure, and could bind to haemoglobin (Hb), no investigation was performed on this possible phenomenon that could affect the APX plasma concentration and thus its pharmacokinetics and pharmacodynamics. We addressed this issue by (1) measuring the levels of APX and haematological/biochemical parameters in 90 patients on APX therapy; (2) assessing the effect of APX on oxygen saturation curves of Hb; (3) testing the direct APX binding to Hb by fluorescence spectroscopy and a zinc-induced precipitation of Hb coupled to a reversed-phase high-performance liquid chromatography (HPLC)-based method; and (4) simulating in silico by molecular docking the APX interaction with human Hb. In a multivariable analysis, Hb was the only independent variable significantly and inversely associated in 90 patients with APX peak plasma level, at variance with patients treated with rivaroxaban (n = 86) and dabigatran (n = 34) therapy. APX causes a progressive left-shift of the oxygen dissociation curve of purified Hb solution, with a Kd ≅300 µM. Fluorescence- and HPLC-based assays concordantly showed that APX binds to Hb with a Kd ≅350 µM. Finally, docking simulations showed that APX can fit into in the central cavity of Hb. These findings support the hypothesis that APX does bind to Hb, which, due to its millimolar concentration in blood, can act as ‘buffer’ for the drug and consequently affect its free plasma level.

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