Differences between the Calculated Fraction Available for BBB Transport and the in Vitro Measured Free Fraction Could be Explained by Capillary Heterogeneity

1996 ◽  
pp. 169-170
Author(s):  
C. Videbæk ◽  
P. Ott ◽  
O. B. Paulson ◽  
G. M. Knudsen
Keyword(s):  
Free Fraction ◽  
Calculated Fraction ◽  
Capillary Heterogeneity

Free Fraction of Valproic Acid: In Vitro Time-Dependent Increase and Correlation with Free Fatty Acid Concentration in Human Plasma and Serum

Epilepsia ◽  
1983 ◽  
Vol 24 (1) ◽  
pp. 65-73 ◽  
Author(s):  
Fiorenzo Albani ◽  
Roberto Riva ◽  
Gaetano Procaccianti ◽  
Agostino Baruzzi ◽  
Emilio Perucca
Keyword(s):  
Valproic Acid ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Human Plasma ◽  
Acid Concentration ◽  
Free Fraction ◽  
Time Dependent ◽  
Fatty Acid Concentration ◽  
Free Fatty Acid Concentration

scholarly journals Correlation between In Vitro and In Vivo Activities of GM 237354, a New Sordarin Derivative, against Candida albicans in an In Vitro Pharmacokinetic-Pharmacodynamic Model and Influence of Protein Binding

2001 ◽  
Vol 45 (10) ◽  
pp. 2746-2754 ◽  
Author(s):  
P. Aviles ◽  
C. Falcoz ◽  
M. J. Guillén ◽  
R. San Roman ◽  
F. Gómez De Las Heras ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Dynamic System ◽  
Equilibrium Dialysis ◽  
Drug Efficacy ◽  
Free Fraction ◽  
Time Curve ◽  
Antifungal Effect ◽  
Immunocompetent Mice

ABSTRACT The antifungal effect of GM 237354, a sordarin derivative, was studied in an in vitro pharmacokinetic (PK)-pharmacodynamic dynamic system (bioreactor) which reproduces PK profiles observed in a previously described model of drug efficacy against murine systemic candidiasis. Immunocompetent mice infected intravenously with 105 CFU of Candida albicans were treated with GM 237354 at 2.5, 10, and 40 mg/kg of body weight every 8 h subcutaneously for 7 days. Free concentrations in serum were calculated by multiplying total concentrations measured in vivo by 0.05, the free fraction determined in vitro by equilibrium dialysis. In the bioreactor the inoculum was ≈106 CFU/ml; and a one-compartment PK model was used to reproduce the PK profiles of free and total GM 237354 in serum obtained in mice, and clearance of C. albicans was measured over 48 h. A good correlation was observed when the in vivo fungal kidney burden and the area under the survival time curve were compared with the in vitro broth “burden,” although only when free in vivo levels in serum were reproduced in vitro. GM 237354 displayed a 3-log decrease effect both in vivo and in vitro. The very few reports available on in vitro-in vivo correlations have been obtained with antibiotics. The good in vitro-in vivo correlation obtained with an antifungal agent shows that the in vitro dynamic system could constitute a powerful investigational tool prior to assessment of the efficacy of an anti-infective agent in animals and humans.

scholarly journals In vitro Model for Studying Interactions between Ketorolac and Omeprazole with Bovine Serum Albumin by UV-Spectroscopic Method

2015 ◽  
Vol 17 (1) ◽  
pp. 92-98 ◽  
Author(s):  
Kanij Nahar Deepa ◽  
Md Khalid Hossain ◽  
Md Shah Amran ◽  
Shaila Kabir
Keyword(s):  
Bovine Serum Albumin ◽  
Serum Albumin ◽  
Binding Site ◽  
Bovine Serum ◽  
Association Constant ◽  
Spectroscopic Method ◽  
Free Fraction ◽  
In Vivo Model ◽  
Specific Probe

The binding of Ketorolac and Omeprazole to bovine serum albumin (BSA) was studied by equilibrium dialysis method followed by UV spectroscopy. Warfarin and Diazepam were used as site-I and site-II specific probe, respectively. The binding of Ketorolac and Omeprazole was characterized by two sets of association constant: high affinity association constant (K1) with low capacity binding site (n1) and low affinity association constant (K1) with high capacity binding site (n1). In this study, n1 and n1 values were found to be 0.25 ± 0.006 and 1.8 ± 0.025 for Ketorolac and 0.22 ± 0.030 and 1.3±0.035 for Omeprazole at pH 7.4 and 37°C, respectively. At the same condition, the values of K1 and K1 for Ketorolac were found to be 0.624 ± 0.033 ?M-1 and 0.133 ± 0.023 ?M-1 and that of Omeprazole were 0.51 ± 0.001 ?M-1 and 0.28 ± 0.005 ?M-1, respectively. Site specific probe displacement studies implied that both Ketorolac and Omeprazole bind predominantly to site-II, the Diazepam site. In the present study, both Ketorolac and Omeprazole increased the free fraction of each other when they simultaneously bound to BSA. They compete for a common binding site on the albumin molecule, thereby free fraction of both the drugs was increased as compared to the level obtained when the drugs were given individually. We, thus, conclude that during concurrent administration of Ketorolac and Omeprazole adequate precautions should be taken. However, further studies are needed on in-vivo model to substantiate the findings from in-vitro experiments. DOI: http://dx.doi.org/10.3329/bpj.v17i1.22323 Bangladesh Pharmaceutical Journal 17(1): 92-98, 2014

Conceptualisation of Diagnostic Agents: From Empirical In Vivo Screening to Rational In Vitro Predictive Parameters

2000 ◽  
Vol 28 (2) ◽  
pp. 303-314 ◽  
Author(s):  
Hafid Belhadj-Tahar ◽  
Rachid Boumahdi ◽  
Marie-hélène Darbieu
Keyword(s):  
Classical Model ◽  
Explanatory Power ◽  
Free Fraction ◽  
Coefficient Of Determination ◽  
In Vivo Screening ◽  
Predictive Parameters ◽  
Diagnostic Agents ◽  
Adsorption Factor

A new rational conceptualisation protocol in new isotopic diagnostic agents has been designed to avoid systematic empirical in vivo screening. This protocol is based on multiple regression analysis, in order to determine the pharmacokinetic model capable of explaining in the best possible way the in vivo behaviour of molecules injected into an organism. Nine technetium complexes (99mTc-L) were synthesised from aminothiol ligand vectors. These complexes were characterised in terms of their physical, chemical and biological in vitro properties, i.e. lipophilicity (P), free fraction unbound to plasmatic proteins (Fup), the fraction unbound to blood cells (FuCb), and membrane adsorption fraction (Fad), an original factor assessed in vitro. Thus, two pharmacokinetic models were tested. The first takes into account the parameters classically used in pharmacokinetics (P, Fup, FuCb), and the second, in parallel with the first, includes the membrane adsorption rate (polar/apolar/polar membrane model). According to the phenomenon of tissular distribution, the explanatory power of the second model, including the Fad, is radically greater than that of the classical model. The comparative adjusted coefficient of determination ([Formula: see text]2) of the model, including the Fad versus [Formula: see text]2 of the first model, are heart (91%/6%), liver (89%/47%), spleen (64%/44%), lung (78%/26%), kidney (70%/33%) and brain (73%/8%), respectively. In addition, as for the myocardium, the membrane adsorption factor seems to be the only predictive factor of the affinity between the myocardium and neutral or cationic molecules. This refutes the generally held view that only cationic molecules could have an affinity with the heart.

Estrogen-induced Changes in Protein Binding of Bupivacaine during in Vitro Fertilization 

1997 ◽  
Vol 87 (4) ◽  
pp. 879-883 ◽  
Author(s):  
Lawrence C. Tsen ◽  
G. Richard Arthur ◽  
Sanjay Datta ◽  
Mark D. Hornstein ◽  
Angela M. Bader
Keyword(s):  
In Vitro Fertilization ◽  
Serum Albumin ◽  
Protein Binding ◽  
Serum Proteins ◽  
Free Fraction ◽  
Vitro Fertilization ◽  
Acid Glycoprotein ◽  
Hormonal Manipulation ◽  
Bupivacaine Toxicity

Background Patients having in vitro fertilization (IVF) procedures that use gonadotropin-releasing hormone agonist down-regulation undergo hormonal manipulation of estrogen concentrations to induce oocyte maturation. After achieving minimal estrogen concentrations (baseline), stimulation increases estrogen concentrations to supraphysiologic levels, leading to egg retrieval. The isolated effect of estrogen on protein binding has not previously been reported. This study was conducted to measure the effect of estrogen concentrations on protein binding of two concentrations of bupivacaine, 1 microg/ml and 5 microg/ml, corresponding, respectively, to systemic concentrations expected after administration of epidural anesthesia and associated with bupivacaine toxicity. Serum proteins were measured to address the mechanism. Methods Twenty-nine healthy women undergoing IVF procedures were enrolled and venous samples were drawn at times of minimal and maximal estrogen concentrations. The percentage of free bupivacaine was determined at fixed concentrations of 1 and 5 microg/ml. Serum albumin and alpha1-acid glycoprotein concentrations were measured at baseline and at retrieval in a group of 24 women. Results The percentage of free bupivacaine increased between times of minimal and maximal serum estrogen concentrations, corresponding to decreased protein binding. Concentrations of serum albumin and alpha1-acid glycoprotein decreased between baseline and retrieval times. Conclusions Patients undergoing IVF procedures demonstrate a decrease in protein binding of bupivacaine from baseline concentrations. These changes may be explained by a decrease in albumin and alpha1-acid glycoprotein. During anesthesia for egg retrieval, clinicians should consider the implications of increased free fraction of drug, especially for highly protein-bound agents.

scholarly journals An endeavor to improve longevity of cryopreserved equine sperm

2017 ◽  
Vol 57 (3) ◽  
pp. 195 ◽  
Author(s):  
TAA KCHALIFA ◽  
M. M. WAHEED ◽  
A. G. LYMBEROPOULOS (Α.Γ. ΛΥΜΠΕΡΟΠΟΥΛΟΣ)
Keyword(s):  
Oxidative Stress ◽  
Bovine Serum Albumin ◽  
Zinc Chloride ◽  
Bovine Serum ◽  
Free Fraction ◽  
Egg Yolk ◽  
Sperm Cells ◽  
Progressive Motility ◽  
In Vitro Effects

Exposure of sperm cells to the oxidative stress pending hypothermic storage of semen has been suggested to be responsible, in part, for the decline of their motility and fertility. This study was conducted to evaluate the in-vitro effects of antioxidants (AOs) and / or caffeine on longevity of cryopreserved stallion spermatozoa. Aliquots from the gel-free fraction of semen ejaculates (n=12), collected from 5 Arabian stallions (9-18 years old) of unknown sperm freezability, were mixed 1:1 with a Tris-egg yolk extender (TEYE), centrifuged at 500 χ g for 5 min and sperm cells were frozen in the form of 0.25-ml concentrated pellets after 2-step addition of TEYE supplemented with or without AOs (0.50 mg /ml Na pyruvate, 1 mg / ml Na thiosulfate, 5 mg / ml bovine serum albumin, 0.15 mg / ml zinc chloride and 0.50 mg / ml ferulic acid). The final pre-freeze concentrations of glycerol and sperm cells were 5% and 562-924 χ IO6 / ml, respectively. Frozen pellets from non-AOs and AOs-treated sperm were thawed in a Tris-citric acidglucose solution (40°C) containing 0, 0.49, 0.97 or 1.94 mg / ml caffeine and incubated (140-230 χ IO6 sperm / ml) at 30°C for 3 h. Sperm progressive motility (%) was assessed after centrifugation, before freezing and after 0, 1, 2 and 3 h of thawing. The results revealed significant (P<0.05) effects of sperm treatments only on post-thaw motility. Neither AOs alone nor caffeine alone could significantly ameliorate the maintenance of sperm motility. AOs plus 0.97 or 1.94 mg / ml caffeine were the superior supplements in improving the longevity of stallion spermatozoa.

Induction of apoptosis of gastric cancer cells SGC7901 in vitro by a cell-free fraction of Tibetan kefir

2013 ◽  
Vol 30 (1) ◽  
pp. 14-18 ◽  
Author(s):  
Jie Gao ◽  
Fengying Gu ◽  
Hui Ruan ◽  
Qihe Chen ◽  
Jie He ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Free Fraction ◽  
Gastric Cancer Cells ◽  
A Cell ◽  
Induction Of Apoptosis

Altered function of pulmonary surfactant in fatty acid lung injury

1990 ◽  
Vol 69 (3) ◽  
pp. 1143-1149 ◽  
Author(s):  
S. B. Hall ◽  
R. H. Notter ◽  
R. J. Smith ◽  
R. W. Hyde
Keyword(s):  
Fatty Acid ◽  
Lung Injury ◽  
Surface Activity ◽  
Pulmonary Surfactant ◽  
Free Fraction ◽  
Phospholipid Content ◽  
Pulmonary Mechanics ◽  
Polymorphonuclear Cells

To determine whether acute fatty acid lung injury impairs pulmonary surfactant function, we studied anesthetized ventilated rabbits given oleic acid (55 mg/kg iv, n = 11) or an equivalent volume of saline (n = 8). Measurements of pulmonary mechanics indicated a decrease in dynamic compliance within 5 min of injury and a decrease in lung volume that was disproportionately large at low pressures, consistent with diminished surfactant activity in vivo. Bronchoalveolar lavage fluid obtained 1 h after injury had significantly increased erythrocytes and total leukocytes, largely polymorphonuclear cells. The phospholipid content and composition of the cell-free fraction had only minor changes from those of controls, but the protein content was increased 35-fold. Measurements of lavage surface activity in vitro showed an increase in average minimum surface tension from 1.3 +/- 0.4 (SE) dyn/cm in controls to 20.2 +/- 3.9 dyn/cm in injured animals. The alterations in static pressure-volume curves and decrease in lavage surface activity suggest a severe alteration of surfactant function in this form of lung injury that occurs despite the presence of normal amounts of surfactant phospholipids.

Ethylene biosynthesis and endogenous polyamines in relation to development of in vitro cultured kiwifruit explants

2004 ◽  
Vol 31 (6) ◽  
pp. 603 ◽  
Author(s):  
Luis Arigita ◽  
Ricardo Sánchez Tamés ◽  
Aida González
Keyword(s):  
Culture Medium ◽  
Free Fraction ◽  
Acc Synthase ◽  
Ethylene Biosynthesis ◽  
Stage Of Development ◽  
Reference Medium ◽  
Polyamine Content ◽  
The Relationship ◽  
Number Of Shoots

The relationship between polyamines and ethylene is controversial because the degree of interference of one pathway with the other may differ according to species, stage of development and experimental procedure. In this paper, we modify ethylene biosynthesis by the addition of aminoethoxyvinylglicine (AVG) or 1-aminocyclopropane-1-carboxylic acid (ACC) and study how it affects polyamine content and development of kiwifruit explants (Actinidia deliciosa CS Liang. & AR Fergusson). Cultured under ventilation where ethylene did not accumulate in the culture vessels, kiwi explants had higher ACC synthase activity and lower polyamine content than those grown without ventilation. In explants cultured in the reference medium, putrescine was the more abundant polyamine and spermine was only detected in the free fraction irrespective of ventilation. Under ventilation, addition of ACC to the culture medium inhibited organogenesis, there was less spermidine and spermine was not detected. Addition of AVG to the culture medium increased both the number of shoots and the amount of polyamines, and inhibited ACC synthase, so S-adenosylmethionine (SAM) led to increasing synthesis of spermidine and spermine. The increase in putrescine is more difficult to explain on the basis of inhibition of ethylene biosynthesis. The increase in the number of shoots in kiwi explants due to AVG addition may be attributed to the lack of ethylene in the atmosphere of the vessels or the increase in free polyamines.

scholarly journals Effect of Phenytoin on Protein Binding of Valproic Acid

1979 ◽  
Vol 6 (4) ◽  
pp. 453-454 ◽  
Author(s):  
J. Bruni ◽  
J.M. Gallo ◽  
B.J. Wilder
Keyword(s):  
Valproic Acid ◽  
Protein Binding ◽  
Acid Concentration ◽  
Equilibrium Dialysis ◽  
Free Fraction ◽  
In Vitro Experiments ◽  
Valproic Acid Concentration ◽  
Acid Protein ◽  
Dialysis Technique

SUMMARY:In vitro experiments using the equilibrium dialysis technique were performed to determine the binding of valproic acid to plasma components in the absence and presence of therapeutic concentrations of phenytoin. The free fraction of valproic acid was found to be dependent on the total valproic acid concentration. Phenytoin did not influence valproic acid protein binding.

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