Serum Alpha 1-acid Glycoprotein Concentrations Research Articles

Oxazepam pharmacokinetics in patients with epilepsy treated long‐term with phenytoin alone or in combination with phenobarbitone.

The pharmacokinetics and serum protein binding of oxazepam, a drug mainly eliminated by a single step glucuronidation reaction, were studied in nine epileptic patients treated long-term with phenytoin or phenytoin with phenobarbitone, and in nine healthy control subjects. Oxazepam elimination half-life was shorter and apparent oral clearance higher in treated patients than in age and sex matched control subjects. Serum bilirubin concentration was lower in treated patients. There was no significant correlation between serum bilirubin concentrations and oxazepam elimination. Serum alpha 1-acid glycoprotein concentration was higher in the treated patients than in the control group. Oxazepam was more than 93% bound to serum proteins, but the extent of binding was not significantly different between the two groups. These results show that oxazepam glucuronyl transferase activity is increased by treatment with phenytoin alone or in combination with phenobarbitone in epileptic patients.

Protein Binding of Doxepin and Desmethyldoxepin

The protein binding of doxepin (DOX) and desmethyldoxepin (DDOX) were studied in serum and plasma samples from healthy volunteers and psychiatric patients. Binding was measured by equilibrium dialysis (16 hrs at 37 degrees) and drug concentrations by radioimmunoassay. In addition, albumin and alpha 1-acid glycoprotein concentrations of the samples were measured by radial immunodiffusion. The mean +/- SEM percentages of unbound DOX were: 20.4 +/- 1.2 and 15.9 +/- 1.2 in healthy subjects (n = 16) and patients (n = 15) respectively, and those of DDOX: 21.4 +/- 0.9 and 19.0 +/- 1.4 for healthy subjects and patients, respectively. There was a significant negative correlation between serum alpha 1-acid glycoprotein concentration and free fraction of DOX in both groups. In healthy subjects a significant negative correlation was also found between albumin concentrations and free fraction of both DOX and DDOX. Binding experiments with isolated protein fractions revealed that all of the total binding in plasma could be explained by binding to albumin and alpha 1-acid glycoprotein. The observed 2--4-fold interindividual variability in the free fractions of these drugs is probably less important than the much larger variability in the total serum concentrations.

Serum alpha-1 acid glycoprotein concentration in pregnancy and with oral contraception

With the use of the technique of single radial immunodiffusion, α1-acid glycoprotein levels were found to be decreased in the sera of pregnant women and in the sera of women ingesting oral contraceptives. Lower levels were detected in cord sera which, in turn, were more marked in the premature infant. As this protein is known to bind progesterone and to be elevated in the presence of tissue destruction or inflammation, sera from premature and toxemic patients were analyzed, but no significant differences in α1-acid glycoprotein concentration were noted when compared to the level encountered in normal term pregnancies.