Liver chronic disease, plasma protein

AED pharmacokinetic data are summarized in Table 52-3. For populations known to have altered plasma protein binding, free rather than total serum concentrations should be measured if the AED is highly protein bound. Conditions altering AED protein binding include chronic renal failure, liver disease, hypoalbuminemia, burns, pregnancy, malnutrition, displac-... 

Albumin has been more extensively studied than any other plasma protein. Among the many reasons for this are the natural abundance of blood plasma, the relatively high stability of albumin, and the early clinical interest in the low plasma albumin levels found in chronic diseases of the kidneys and liver (E5, M32). Prominence was at one time given to the role of albumin as a regulator of tissue fluid balance and an inhibitor of edema... 

A number of studies have examined RBP levels (and usually TTR and vitamin A levels as well) in patients with various kinds of acute and chronic diseases of the liver (Smith and Goodman, 1971 Kindler, 1972 Prellwitz et al., 1974 Skredeeta/., 1975 Brissot er a/., 1978 Vahlquist a/., 1978a Russell et a/., 1978 McClain et al., 1979). In patients with clinically significant hepatic parenchymal disease, the plasma levels of vitamin A, RBP, and TTR have usually been found to be substantially depressed. The low levels of RBP and TTR presumably reflect a reduced rate of production of the proteins by the diseased liver. 

Albumin has a molecular mass of approximately 66 000 and is synthesized at a rate of about 12 g, equal to 3% of total body albumin, per day to replace that which is degraded or lost. Impaired albumin synthesis and therefore a low plasma albumin concentration, is a hallmark of chronic liver disease. Several functions can be ascribed to albumin including osmotic (oncotic) pressure regulation of the plasma and a non-specific transport protein for ligands such as calcium, fatty acids, drugs and bilirubin. 

Pharmacokinetics Poorly absorbed from the G1 tract. Protein binding greater than 98%. Metabolized in the liver. Minimally eliminated in urine. Plasma levels are markedly increased in chronic alcoholic hepatic disease, but are unaffected by renal disease. Half-life 14 hr. 

In patients with acute hepatitis and active hepatitis, protein binding of the glucocorticoids will be reduced and peak concentrations of administered glucocorticoids increased. Conversion of prednisone to prednisolone has been reported to be impaired in chronic active liver disease (409). However, although plasma prednisolone concentrations were more predictable after the administration of prednisolone than of prednisone to a group of healthy subjects (410), there was no difference in patients with chronic active hepatitis. There was also impaired elimination of prednisolone in these patients. In a review of the pharmacokinetics of prednisone and prednisolone it was concluded that fear of inadequate conversion of prednisone into prednisolone was not justified (411). Patients with hepatic disease suffer adrenal suppression more readily (111). 

Perez-Mateo, M. Erill, S. (1977) Protein binding of salicylate and quinidine in plasma from patients with renal failure, chronic liver disease and chronic respiratory insufficiency. European Journal of Clinical Pharmacology, 11, 225-231. 

Decreased Plasma Levels. Transferrin is a negative APR the most common cause of low levels is inflammation or malignancy. Decreased synthesis is seen with chronic liver disease and malnutrition (see Chapter 47). Protein loss, as in the nephrotic syndrome or protein-losing enteropathies, also results in low levels. In hereditary atrans-ferrinemia, a very low level of Tf is accompanied by iron overload but severe hypochromic anemia resistant to iron therapy. 

Total RBP measurements, however, are indicative of plasma levels of vitamin A under most survey conditions and would be equivalent to direct vitamin A determination for assessment purposes, providing the population excludes those suffering from relatively short-term or chronic severe calorie and/or protein deficit and those suffering from diseases (e.g., of the liver) that will affect RBP levels (see Chapter 7). Currently there has been no report of a large-scale survey in which both parameters have been measured to determine their comparability as assessment tools for vitamin A nutriture. Reddy et al. (1979) found children with mild forms of PEM had values for both RBP and retinol similar to normal children. 

---