Albumin, plasma protein binding

Certain other plasma proteins bind heme but not hemoglobin. Hemopexin is a Pj-globuhn that binds free heme. Albumin wiU bind some metheme (ferric heme) to form methemalbumin, which then ttansfets the metheme to hemopexin. 

Sawada and coworkers [25-27] studied the iso-pH 7.4 MDCK permeabilities of very lipophilic molecules, including chlorpromazine (CPZ) [25], These authors included 3% wt/vol bovine serum albumin (BSA) on the apical (donor) side, and 0.1-3% BSA on the basolateral (acceptor) side, and found that plasma protein binding greatly affected the ability of molecules to permeate cellular barriers. They observed cell tissue retention of CPZ ranging from 65 to 85%, depending on the... 

These refinements in our knowledge of brain penetration and CNS activity of drugs feature prominently in a major medicinal review of the blood-brain barrier [14]. In vivo perfusion studies on the rate of brain uptake of several non-steroidal anti-inflammatory drugs in rats with increasing concentration of albumin in the perfusate clearly demonstrate the effect of plasma protein binding on the rate (in addition to the extent at steady-state) of brain uptake [15]. 

There have been several studies that underscore the importance of unbound concentration in cell-based studies of receptor function. In a model study of the effect of plasma protein binding on the renal transport of organic anions using the expression of various organic anion transporters (OATPs) in Xenopus oocytes, the transport of ochratoxin A, methotrexate, and estrone sulfate was found to be strongly inhibited by the addition of human serum albumin to the culture medium [16]. Similarly, the addition of oq-acid glycoprotein was found to reverse the blockade of sodium-ion current by cocaine in a preparation of cardiac myocytes [17]. 

There have been several reports where plasma protein binding data was used in the prediction of in vivo properties of compounds. Two papers noted that the ability to predict in vivo clearance from in vitro microsome data was greatly improved when a plasma protein binding term was included [64,65]. In another study, binding to phospholipids and human serum albumin was assessed by HPLC retention times (on IAM and HAS columns, respectively) and used to predict volume of distribution [66]. 

Plasma contains a large variety of proteins, all of which have the potential to interact with drugs. Albumin is generally considered to be the most important contributor to the plasma protein binding of drugs (GIO, Gil, M16), but for some, e.g., steroids, other proteins play a major role. 

Pharmacokinetics Entacapone is rapidly absorbed, with a T ax of approximately 1 hour. The absolute bioavailability following oral administration is 35%. The plasma protein binding of entacapone is 98%, mainly to serum albumin. Entacapone is almost completely metabolized prior to excretion, with only a small amount (0.2% of dose) excreted in the urine. 

Absorption/Distribution - Bioavailability depends on an acidic pH for dissolution and absorption. In vitro, plasma protein binding is approximately 95% to 99%, mainly to albumin. 

The plasma protein binding of tacrolimus is approximately 99%. Tacrolimus is bound mainly to albumin and alpha-1-acid glycoprotein and has a high level of association with erythrocytes. It is extensively metabolized by the mixed-function oxidase system, primarily the cytochrome P450 system (CYP3A). The disposition of tacrolimus from whole blood was biphasic with a terminal elimination half-life of 11.7 hours in liver transplant patients. 

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