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Biomedical subjects

J H Perrin

Publications and source records attributed to J H Perrin.

At least 55 records · Page 3Linked to original sources
PubMed1980

The effect of albumin conformation on the binding of warfarin to human serum albumin. The dependence of the binding of warfarin to human serum albumin on the hydrogen, calcium, and chloride ion concentrations as studied by circular dichroism, fluorescence, and equilibrium dialysis.

The pH dependence of the binding of warfarin to human serum albumin has been studies by circular dichroism, fluorescence, and equilibrium dialysis. The pH dependences of the induced ellipticity and the fluorescent intensity of the warfarin . albumin complexes at low drug to protein ratios parallel the neutral to base transition, occurring in the protein over the pH range 6 to 9. Dialysis data show albumin to have a single high affinity site for warfarin over this pH range. This affinity is higher for the basic than for the neutral conformation. Calcium ions increase the high affinity constant of warfarin for albumin over the same pH region, by affecting the neutral to base transition. On the other hand, chloride ions reduce the induced ellipticity and the fluorescent intensity of the complexes at all pH investigated, the mechanism being primarily that of displacement of the drug from albumin.

Binding Sites↗
PubMed1980

Investigations into the binding of phenprocoumon to albumin using fluorescence spectroscopy.

The fluorescence of phenprocoumon is enhanced following interaction with bovine and human serum albumin, allowing the binding parameters for two binding sites to be estimated by a modified Bjerrum method and the Scatchard method. The fluorescence is increased as the pH is raised to 9.0 and also on addition of the drugs ibuprofen and fenoprofen. Chloride ions, phenylbutazone and acenocoumarin seem to displace phenprocoumon from its primary binding site on human serum albumin. Investigations with the enantiomers of phenprocoumon show that the binding sites have some stereospecificity.

4-Hydroxycoumarins↗
PubMed1979

Conformational changes in human serum albumin around the neutral pH from circular dichroic measurements.

The molar ellipticity of the warfarin-albumin complex at 310 nm increases with pH from 6 to 9. This pH dependence runs parallel with that of the molar ellipticity of the albumin alone at 292 nm. The change in molar ellipicity with pH occurs in a smaller pH interval after addition of the physiological concentration of calcium ions. These findings give support to the assumption that the binding site for warfarin on the albumin molecule is affected by the neutral-to-base transition in the protein.

Binding Sites↗
PubMed1979

Hemodialysis of theophylline in uremic patients.

Hemodialysis of theophylline was studied in three uremic patients. The dialysis clearance ranged from 75.6 to 97.9 ml/min and averaged 88.1 ml/min. A much smaller value of 32.8 ml/min was reported by Levy and associates. The difference may be attributed to the two monitoring factors during hemodialysis, namely, blood and dialyzate flow rates. Both were higher in our study. Analysis of the semilogarithmic plots of the arterial plasma concentration versus time over a 3-hour period gave apparent half-lives of 3.15, 2.04, and 2.73 hours, respectively, for the three patients. Half-life of theophylline in normal subjects ranged from 4 to 6 hours or even longer. A prolonged half-life of theophylline in uremia could be expected. Our kinetic study indicated an approximately 50 per cent reduction in terminal half-life during hemodialysis. Hourly dialyzate was collected from one patient to account for drug recovery in the dialysis fluid. Forty per cent of the administered dose was recovered in the dialyzate during a 3-hour dialysis period, indicating effective removal. Dialysis clearance for creatinine was calculated by arterial-venous difference and correlated with that of theophylline. We found that theophylline was cleared by the dialyzer at a rate approximating 63 per cent of creatinine removal.

Adult↗
PubMed1978

beta-Cyclodextrin as an aid to peritoneal dialysis. Renal toxicity of beta-cyclodextrin in the rat.

A peritoneal dialysate containing beta-cyclodextrin has been shown to accelerate the removal of intravenously administered phenobarbital in rats. It was found that high concentrations of beta-cyclodextrin were toxic to the animals in the single exchange technique employed. The renal toxicity was estimated by measuring blood urea nitrogen values in the rats following oral and intraperitoneal administration of the cyclic amylose.

Amylose↗
PubMed1977

Oxidation kinetics of phenothiazine and 10-methylphenothiazine in acidic medium.

The rate of phenothiazine degradation in an acidic oxygen-saturated medium was studied. 3H-Phenothiazine-3-one and phenothiazine 5-oxide are produced by parallel reactions, and 7-(10'-phenothiazinyl)-3H-phenothiazine-3-one is produced in a more complex manner. The overall phenothiazine degradation rate appears to be pH independent up to pH 7.0. The degradation kinetics of 10-methylphenothiazine were studied after isolation and identification of its degradation products, 10-methylphenothiazine 5-oxide and 3H-phenothiazine-3-one. The main degradation product is 10-methylphenothiazine 5-oxide; but at low pH values and high temperatures, more 3H-phenothiazine-3-one is formed. The degradation rate of 10-methylphenothiazine is pH independent up to pH 7.

Drug Stability↗
PubMed1977

Mechanism for phenothiazine oxidation.

The mechanism of phenothiazine degradation was studied by following the degradation of 3,10'-diphenothiazine in ethanol-water mixtures as well as the electrochemical oxidation of phenothiazine. A mechanism, including the formation of an oxidized dimer and some polymers, is suggested.

Electrochemistry↗
PubMed1977

Quantitative correlations between albumin binding constants and chromatographic Rm values of phenothiazine derivatives.

The binding constants of 15 phenothiazine derivatives to bovine serum albumin were obtained by a circular dichroic probe technique; The lipophilicity of the drugs, measured by a reversed-phase thin-layer technique using oleyl alcohol and methanol-water mixtures as the solvents, is expressed as RMw. The binding constants were of the same order of magnitude as the literature values, and the RMw values correlated well with log P octanol values from the literature. Correlations of log K with RMw were found to be more satisfactory when corrections for the state of ionization of the phenothiazines were made, the nonprotonated species accounting for the bulk of the binding. A better correlation was obtained when contributions from both species were taken into account. Similar correlations were attempted between RMw values and enzyme inhibitory activities of these phenothiazines taken from the literature.

Binding Sites↗
PubMed1976

Chromatographic characterization of phenothiazine drugs by a reversed-phase thin-layer technique.

A reversed-phase thin-layer chromatographic technique was used for the characterization of 26 phenothiazine drugs. With two chromatographic systems having the sam stationary phase and phase volume ratio, but mobile phases of different pH, all but two of the compounds could be identified. Rf values in the different systems were standardized by applying a reference compound to the plates next to each compound under investigation; the corrected Rf values were calculated from the differences in the Rm values of the compounds and the reference compound, and the theoretical Rm value of the reference. It was shown that Rf values for different chromatographic systems with the same stationary phase could be predicted with reasonable accuracy. The pH of the mobile phase, for which a maximum difference in Rf values was obtained for pairs of compounds, could also be calculated and corresponded well with the observed values.

Adsorption↗
PubMed1976

A comparison of the determination of partition coeficients of 1,4-benzodiazephines by high-performance liquid chromatography and thin-layer chromatography.

Relative partition coefficients (P) of 1,4-benzodiazepines were determined by a reversed-phase thin-layer chromatographic (RP-TLC) technique in the systemoleyl alcohol-water, and by high-performance liquid chromatography (HPLC) using several column packing materials. RMw values, obtained by RP-TLC, correlated well with log P values determined directly in the system oleyl alcohol-water and with the literature values for the system 1-octanol-water. Th log k' w values from the HPLC experiments could be determined with greater precision, but the correlations of log k'w with log Poleyl alcohol and log Poctanol were not as good as those found for the Rmw values.

Benzodiazepines↗