Diffusion of Drugs into Prostatic Fluid and Milk

1974 ◽  
Vol 8 (8) ◽  
pp. 470-475 ◽  
Author(s):  
Eric J. Lien ◽  
Jean Kuwahara ◽  
Robert T. Koda
Keyword(s):  
Protein Binding ◽  
Partition Coefficient ◽  
Blood Circulation ◽  
Antibacterial Agents ◽  
Log P ◽  
Clinical Implications ◽  
Degree Of Dissociation ◽  
Ph Values ◽  
Prostatic Fluid ◽  
Plasma Concentration Ratio

THE PROSTATIC FLUID/PLASMA CONCENTRATION RATIO of various sulfonamides, antibiotics and antibacterial agents, and the milk/plasma ratio of sulfonamides and basic drugs have been quantitatively correlated with the degree of dissociation, as represented by log U/D, and the partition coefficient (log P). Because of the lower pH values of the prostatic fluid (6.6) and milk (6.8) as compared with the plasma pH (7.4), the degree of dissociation appears to be the most important factor in determining the distribution of these weak acids or bases. Partition coefficient also plays a secondary role. The log Po for maximum diffusion into milk is lower than that for maximum gastrointestinal, buccal or percutaneous absorption. This may be attributed to plasma protein binding which prevents diffusion of the drug from the blood circulation into the milk since high lipophilicity favors protein binding. The clinical implications of the correlations obtained are discussed.

THE EFFECTS OF CALCIUM ON PROTEIN-BINDING AND METABOLISM OF ARGININE VASOPRESSIN IN RATS

1965 ◽  
Vol 32 (2) ◽  
pp. 141-151 ◽  
Author(s):  
M. W. SMITH ◽  
N. A. THORN
Keyword(s):  
Protein Binding ◽  
Calcium Chloride ◽  
Blood Volume ◽  
Arginine Vasopressin ◽  
Binding Sites ◽  
Blood Concentration ◽  
Blood Circulation ◽  
Volume Of Distribution ◽  
Rat Serum

SUMMARY Hypercalcaemia produced in rats by the intravenous injection of calcium chloride, slowed the rate of disappearance of injected vasopressin from the blood circulation. 24% of the vasopressin injected appeared in the urine of hypercalcaemic rats compared with 7 % in control animals. Vasopressin injected intravenously into control rats was distributed in a volume equal to the blood volume but when rats had been made hypercalcaemic, the theoretical volume of distribution was three to four times greater. Antidiuresis produced by injection of large doses of vasopressin into hydrated rats was little affected by changes in the blood concentration of calcium. Calcium chloride injected intravenously into hydrated rats resulted in a temporary antidiuresis. Experiments in vitro with Sephadex G-25 showed that both ox neurophysin and rat serum protein bind vasopressin and that calcium interferes with the binding. It is suggested that calcium can compete directly with vasopressin for acidic binding sites on proteins; that this can cause the release of vasopressin and alter the transport and possibly the rate of inactivation, of vasopressin.

scholarly journals The apparent permeabilities of Caco-2 cells to marketed drugs: magnitude, and independence from both biophysical properties and endogenite similarities

2015 ◽  
Author(s):  
Steve O'Hagan ◽  
Douglas B Kell
Keyword(s):  
Partition Coefficient ◽  
Molecular Similarity ◽  
Phospholipid Bilayer ◽  
Log P ◽  
Biophysical Properties ◽  
Apparent Permeability ◽  
Endogenous Metabolites

We bring together fifteen, nonredundant, tabulated collections (amounting to 696 separate measurements) of the apparent permeability (Papp) of Caco-2 cells to marketed drugs. While in some cases there are some significant interlaboratory disparities, most are quite minor. Most drugs are not especially permeable through Caco-2 cells, with the median Papp value being some 16.10-6 cm.s-1. This value is considerably lower than those (1310 and 230.10-6 cm.s-1) recently used in some recent simulations that purported to show that Papp values were too great to be transporter-mediated only. While these values are outliers, all values, and especially the comparatively low values normally observed, are entirely consistent with transporter-only mediated uptake, with no need to invoke phospholipid bilayer diffusion. The apparent permeability of Caco-2 cells to marketed drugs is poorly correlated with either simple biophysical properties, the extent of molecular similarity to endogenous metabolites (endogenites), or any specific substructural properties. In particular, the octanol:water partition coefficient, log P, shows negligible correlation with Caco-2 permeability. The data are best explained on the basis that most drugs enter (and exit) Caco-2 cells via a multiplicity of transporters of comparatively weak specificity.

Apparent octanol/water partition coefficients of pentachlorophenol as a function of pH

1982 ◽  
Vol 60 (16) ◽  
pp. 2104-2106 ◽  
Author(s):  
Klaus L. E. Kaiser ◽  
Ilze Valdmanis
Keyword(s):  
Aqueous Solution ◽  
Ionic Strength ◽  
Partition Coefficient ◽  
Linear Function ◽  
Partition Coefficients ◽  
Extreme Values ◽  
Log P ◽  
Water Partition Coefficient ◽  
Non Linear ◽  
Good Agreement

The apparent 1-octanol/water partition coefficient (log PApp) of pentachlorophenol (PCP) varies in non-linear function with pH of the aqueous solution. In the range of pH 1.2 to 13.5 extreme values of log PApp 4.84 at pH 1.2 and log PApp 1.3 at pH 10.5 were observed. In the alkaline regime, log PApp increases strongly with the ionic strength. The ion-corrected partition coefficient of PCP was found to be log P 5.05 in good agreement with literature values.

Influence of the physicochemical environment on membrane-protein binding: investigation using a fabricated PVDF membrane

2015 ◽  
Vol 35 (4) ◽  
pp. 339-347
Author(s):  
Abdul L. Ahmad ◽  
Norhidayah Ideris ◽  
Ooi Boon Seng ◽  
Low Siew Chun ◽  
Asma Ismail
Keyword(s):  
Membrane Protein ◽  
Protein Binding ◽  
Polyvinylidene Fluoride ◽  
Pvdf Membrane ◽  
Ph Values ◽  
Symmetric Structure ◽  
Binding Mechanisms

Abstract The correlation between the behavior of a polyvinylidene fluoride (PVDF) membrane toward protein binding at different physicochemical environments was investigated. The PVDF membrane was first fabricated and characterized to understand its morphological, polymorph and intrinsic characteristics. The results confirmed that the membrane had a microporous, symmetric structure and high hydrophobicity and electronegativity. The membrane was further tested under different physicochemical environments by modifying the type of protein and pH medium used. The results showed that different proteins and pH values contribute to different membrane-protein binding mechanisms. Overall, the results of PVDF membrane-protein binding were satisfactory and demonstrated the ability of the membrane to capture various proteins or reagents.

Determination of Ionization Constant (pKa) and Octanol–Water Partition Coefficient (Log P) of Cyclopiazonic Acid

2005 ◽  
Vol 88 (5) ◽  
pp. 1367-1370 ◽  
Author(s):  
Victor S Sobolev
Keyword(s):  
Partition Coefficient ◽  
Potentiometric Titration ◽  
Ionization Constant ◽  
Cyclopiazonic Acid ◽  
Log P ◽  
Experimental Conditions ◽  
Water Partition Coefficient

Abstract The ionization constant (pKa) and the octanol–water partition coefficient (log P) of the important mycotoxin cyclopiazonic acid (CPA) were determined by means of potentiometric titration, and the lipophilicity profile (log D) was calculated. Under the experimental conditions, pKa of CPA = 2.97 ± 0.09, log P = 3.83 ± 0.10, and log D at pH 7.4 = −0.58.

scholarly journals Actual solubility (S|real.|), level of hydrophilic-lipophilic balance (HLBRequ., HLBD, HLBG) and partition coefficient (log P) of phytochemicals contained in Ext. Camellia sinensis L. aqu. siccum in the light of general Hildebrand-Scatchard-Fedors theory of solubility

2018 ◽  
Vol 64 (2) ◽  
pp. 46-59 ◽  
Author(s):  
Zbigniew Marczyński ◽  
Beata Skibska ◽  
Sławomira Nowak ◽  
Jerzy Jambor ◽  
Marian Mikołaj Zgoda
Keyword(s):  
Partition Coefficient ◽  
Phase Boundary ◽  
Green Tea ◽  
Camellia Sinensis ◽  
Mass Exchange ◽  
Selective Extraction ◽  
Optimal Choice ◽  
Log P ◽  
Correlation Equations ◽  
Hydrophilic Lipophilic Balance

Summary Introduction: Using the general Hildebrand-Scatchard-Fedors theory of solubility, the mole fraction (x2) of solubility of phytochemicals contained in the dry green tea leaves was calculated which determines the profile of pharmacological activity. Objective: The applicative purpose of the study was to estimate the actual solubility of phytochemicals – S|real.| [mol/dm3] in water and in water-ethanol solutions of diversified polarity (εM) for their selective extraction and optimal formulation of oral solid dosage form. Methods: The basic physico-chemical and structural quantities of phytochemicals and corresponding mathematical equations of general Hildebrand-Scatchard-Fedors theory of solubility were used to calculate the actual solubility – S|real.| and the level of hydrophilic-lipophilic balance (HLB). Results: The calculated actual solubility values – S|real.| [mol/dm3] collated with correlation equations enabled the assessment of phytochemical capability for the process of mass exchange on phase boundary. Correlation equations for the dependence log P = f (– log S|real.|) point to the structural preferences of phytochemicals in the kinetics of the mass exchange (diffusion) through the natural phase boundary. Conclusions: Calculations and correlations between the values characterizing the actual solubility – S|real.|, media polarity (water, ethanol and their solutions) and the partition coefficient (log P) including the level of hydrophilic-lipophilic balance (HLB) show that basing on thermodynamic components of the general Hildebrand-Scatchard-Fedors theory of solubility, the diffusion profile of phytochemicals contained in the green tea extract (Ext. Camellia sinensis L. aqu. siccum) through the biological phase boundary as well as optimal choice of the extraction medium for selective extraction of the class of phytochemicals can be estimated.

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