Biomedical subjects

H L Behm

Publications and source records attributed to H L Behm.

5 recordsLinked to original sources

PubMed1981

Parabolic equation relating free and total drug concentrations in cases of nonlinear plasma protein binding.

In many cases of nonlinear drug-protein binding, investigators have fitted data to the classical Langmuir model with two classes of binding sites involving four parameters. For human serum albumin binding of tolmetin and salicylate, a simple two-parameter parabolic equation relating free to total concentrations fitted the binding data better. Thus, the free fraction corresponding to the serum or plasma drug concentration in the blood sample taken from a subject can be estimated directly from the parabolic model. This is not the case when the Langmuir model is used to describe nonlinear binding data since the positive root of a cubic equation must be obtained to estimate the free from the total concentration. The direct relationship between free and total drug concentrations would be useful in many clinical situations.

Blood Proteins↗

PubMed1981

Free fraction change with differing volume ratios in equilibrium dialysis: cases of non-linear drug-protein binding.

When equilibrium dialysis is used to measure drug-protein binding, an increase in the volume ratio (buffer solution/protein solution) causes a decrease in the total drug concentration at equilibrium. When binding is non-linear, this decrease in total drug-concentration also causes a decrease in the free fraction. By use of the same volume ratio (3:1) binding curves were obtained for the binding of prednisolone to plasma proteins, and for the binding of salicylic acid and tolmetin to human serum albumin (HSA). When the volume ratio was changed, the observed free fractions were appreciably different from those expected by taking into account only the changes in the total equilibrium drug concentration. There is evidence that this phenomenon is the result of competition for binding sites between the drug and an impurity in the HSA. The effects are not the result of the presence of free fatty acids.

Blood Proteins↗

PubMed1980

Oral and intravenous bretylium disposition.

To compare the oral and intravenous disposition of bretylium tosylate in man, 10 normal male subjects were randomly assigned single doses of 5 mg/kg bretylium tosylate either orally or intravenously and crossed over 2 wk later to the opposite route (20 studies). Each experiment included sampling for drug in serum and urine over 48 hr. Bretylium tosylate was assayed by gas chromatography. Kinetic analysis provided the following mean [coefficient of variation] results: 100FPo, 22.6% [40.2%]; ClrIV, 300 ml/min [27.8%]; ClrPo, 1.268 mg/min [54.8%]; ClBIV, 299 ml/min [31.9%]; f, 101% [8.7%]; Vdss, 3.37 l/kg [30.5%]; lambda lIV 0.0510 [12.8%]; lambda lPG, 0.115 [52.7%]hr-1; elimination half-life (t 1/2) after intravenous bretylium tosylate, 13.6 hr, and after oral bretylium tosylate, 6.0 hr (harmonic means). Bretylium tosylate binding to plasma proteins in normal volunteer samples was found to be negligible. The results indicate extensive tissue binding of bretylium tosylate. Oral doses of bretylium tosylate are only partially absorbed. Bretylium tosylate is eliminated entirely by the kidneys as unchanged drug. The greater renal clearance after oral than intravenous bretylium tosylate, and the greater elimination rate constant and shorter oral bretylium tosyulate t 1/2 are of interest but no explanation is available.

Administration, Oral↗

PubMed1979

Errors in interpretation of data from equilibrium dialysis protein binding experiments.

In equilibrium dialysis protein binding experiments, the fraction of free or bound drug determined at equilibrium by dialysis of a patient plasma sample does not correspond to the drug concentration in the initial plasma sample, but to the drug concentration inside the plasma compartment of the dialysis apparatus at equilibrium. That fraction of free or bound drug corresponds to a lower total drug concentration than that in the initial plasma sample because of loss of drug due to passage of free drug into the buffer compartment in the equilibrium dialysis experiment. The magnitude of the difference between the initial drug concentration and the equilibrium drug concentration depends on the extent of drug binding and experimental conditions. If the initial total drug concentration in the plasma or serum sample as well as the fraction of drug bound at equilibrium as determined by radiotracer methods are known, then, using methods given in the text, the equilibrium drug concentration, the binding parameters corresponding to equilibrium conditions, and the free drug concentration in the initial plasma sample may be estimated.

Blood Proteins↗

PubMedDate not supplied

Binding of tolmetin and salicylic acid to human serum albumin as a function of temperature.

When drug-protein binding data are evaluated thermodynamically standard free energy (delta G0), standard enthalpy (delta H0) and standard entropy (delta S0) are usually estimated from association constants (Ka) derived from binding data obtained at only two temperatures. Estimation of delta H0 involves the assumption of its constancy in the temperature range studied and linearity of a van't Hoff plot of ln Ka versus 1/T. Sometimes the assumption of such linearity is invalid for theoretical reasons and data obtained at only two temperatures contain no information concerning linearity of this plot. We present data for the binding of both tolmetin and salicylic acid to human serum albumin as a function of temperature which make doubtful the validity of using association constants of these drugs to derive thermodynamic constants other than delta G0 values.

Binding Sites↗