What are the pharmacokinetics and pharmacodynamics of albumin?

From the Guidelines

Albumin is a crucial protein with significant pharmacokinetic and pharmacodynamic properties, and its use should be guided by the most recent and highest quality evidence to optimize patient outcomes in terms of morbidity, mortality, and quality of life. When considering the pharmacokinetics and dynamics of albumin, it is essential to understand its synthesis, distribution, and catabolism. Albumin is synthesized primarily in the liver at a rate of about 10-15 grams per day, with a normal plasma concentration of 3.5-5.0 g/dL 1. Pharmacokinetically, albumin has a half-life of approximately 20 days and distributes throughout the intravascular space, making up about 50% of plasma proteins 1. It undergoes minimal renal excretion due to its large molecular weight (66.5 kDa), and is primarily catabolized in the liver and other tissues 1. Pharmacodynamically, albumin serves multiple crucial functions: it maintains oncotic pressure in the bloodstream, preventing fluid leakage into tissues; acts as a transport protein for numerous substances including drugs, hormones, fatty acids, and bilirubin; provides antioxidant effects through free radical scavenging; and exhibits buffer capacity to help maintain blood pH 1. When administered therapeutically as human albumin solution (typically 5% or 25% concentrations), it expands plasma volume and is used in conditions like hypovolemia, shock, burns, hypoalbuminemia, and certain liver diseases 1. The volume expansion effect is dose-dependent, with 5 grams of albumin drawing approximately 75 mL of fluid into the intravascular space 1. The most recent and highest quality study recommends the use of intravenous albumin in patients with spontaneous bacterial peritonitis (SBP) at a dose of 1.5 g/kg at day 1 and 1 g/kg at day 3, in addition to antibiotics, as it has been shown to reduce the risk of acute kidney injury (AKI) and mortality in these patients 1. However, it is essential to note that albumin should not be used in patients with cirrhosis and uncomplicated ascites, unless associated with AKI, as it has not been shown to reduce the risk of AKI or mortality in these patients and may be associated with more pulmonary edema 1. In summary, understanding albumin's pharmacokinetics and dynamics is crucial for its appropriate clinical use, and its administration should be guided by the most recent and highest quality evidence to optimize patient outcomes. Key points to consider when using albumin include:

• Its pharmacokinetic properties, such as its half-life and distribution
• Its pharmacodynamic properties, such as its effects on oncotic pressure and drug binding
• The dose-dependent volume expansion effect
• The specific indications for its use, such as SBP and hypoalbuminemia
• The potential risks and benefits associated with its use, such as fluid overload and pulmonary edema.

From the FDA Drug Label

Plasbumin-25 is hyperoncotic and on intravenous infusion will expand the plasma volume by an additional amount, three to four times the volume actually administered, by withdrawing fluid from the interstitial spaces, provided the patient is normally hydrated interstitially or there is interstitial edema. The pharmacokinetics of albumin are not directly described in the provided drug labels. However, the pharmacodynamics of albumin can be described as:

• Volume expansion: Albumin expands plasma volume by withdrawing fluid from interstitial spaces.
• Oncotic activity: Albumin has positive oncotic activity, which can help maintain plasma colloid osmotic pressure.
• Hemodilution: Albumin can cause hemodilution, which persists for many hours in patients with reduced circulating blood volume. The dosage of albumin varies depending on the indication, but the total dose should not exceed the level of albumin found in a normal individual, approximately 2 g per kg body weight 2.

From the Research

Pharmacokinetics of Albumin

• Albumin is a simple protein present in animal and plant physiological fluids and tissues, playing many important roles including maintenance of appropriate osmotic pressure, binding and transport of various substances like hormones, drugs, etc. in blood, and neutralisation of free radicals 3.
• The biological effects of albumin in critical illness are incompletely understood, but may enhance its clinical role beyond use as an intravenous fluid 4.
• Albumin preparations obtained by separation of human plasma are used clinically for more than 50 years to reverse hypoalbuminemia and to allow for reversal of abnormalities in substance transport 3.

Dynamics of Albumin

• Albumin plays a key role in the homeostasis of vascular endothelium, offering protection from inflammation and damage to the glycocalyx 4.
• Albumin binds a diverse range of compounds, transporting, delivering, and clearing drugs, and helping with uptake, storage, and disposal of potentially harmful biological products 4.
• The main evidence-based indication for albumin administration is liver disease, and it is also used for fluid replacement in plasmapheresis and liver diseases, including hepatorenal syndrome, spontaneous bacterial peritonitis, and large-volume paracentesis 5.

Clinical Use of Albumin

• Albumin is used as a second-line and adjunctive to crystalloids for fluid resuscitation in hypovolemic shock, sepsis and septic shock, severe burns, toxic epidermal necrolysis, intradialytic hypotension, ovarian hyperstimulation syndrome, major surgery, non-traumatic brain injury, extracorporeal membrane oxygenation, acute respiratory distress syndrome, and severe and refractory edema with hypoalbuminemia 5.
• However, routine supplementation of 5% human albumin to maintain a serum albumin level ≥ 20 g/L in burn patients is expensive and provides no benefit 6.
• Implementation of evidence-based guidelines in hospitals can be an effective measure to reduce inappropriate uses of albumin 5.