The plasma protein binding of basic drugs.

Abstract

The plasma protein binding of basic drugs appears to vary more than was at first assumed and is related to the marked intra‐and interindividual differences in one of the chief binding proteins, AAG. Changes in AAG concentrations will result in alterations in the distribution and metabolism of basic drugs which will complicate the interpretation of the relationship between total drug concentration and drug efficacy or toxicity. For some drugs, e.g. lignocaine, direct measurement of free concentrations may improve their clinical use but rapid and reliable techniques are as yet not readily available.

A comparison of drug protein binding and alpha 1‐acid glycoprotein concentration in Chinese and Caucasians.

“…Our finding of similar binding of warfarin and other studies which also examined diazepam and salicylic acid binding (Ghoneim et al, 1981;Zhou et al, 1990), suggest that this interethnic difference does not extend to acidic drugs that are primarily bound to either sites I or II on albumin. A large number of basic drugs including antiarrhythmics, antidepressants, opiates and P-adrenoceptor blockers are primarily bound by AAG (Routledge, 1986). AAG concentration shows a wide variation in health and disease.…”

Plasma protein binding of amiodarone in a patient population: measurement by erythrocyte partitioning and a novel glass‐binding method.

“…There was no difference in binding between control subjects and patients, indicating that the binding was unaffected by the presence of the other drugs taken (see patient details in Methods). Not unexpectedly, the fraction bound did not vary with albumin levels, since other proteins, especially a,-acid glycoprotein, are more important ligands for hydrophobic basic drugs (Routledge, 1986). This protein was not measured in the present study, but its levels are known to vary widely with disease and future investigations should examine the effect of changing levels of this critical protein on amiodarone binding.…”

Disopyramide protein binding in plasma from patients with nephrotic syndrome during the exacerbation and remission phases.

“…In this context, we recommend that AAG levels should be frequently monitored in severe nephrotic patients with rapidly changing clinical status to whom disopyramide is to be prescribed. This consideration might be valid for other basic drugs of which the major binding protein is AAG (Piafsky, 1980;Routledge, 1986).…”