Plasma proteins, drug binding

Cisplatin shows biphasic plasma decay with a distribution phase half-life of 25 to 49 minutes and an elimination half-life of 2 to 4 days. More than 90% of the drug is bound to plasma proteins, and binding may approach 100% during prolonged infusion. Cisplatin does not cross the blood-brain barrier. Excretion is predominantly renal and is incomplete. 

It is well known that drugs bind to plasma proteins, particularly to serum albumin and a-acid glycoprotein, and that only the unbound, or free, fraction is responsible for any pharmacological effect. For protein-drug binding studies size-exclusion chromatography in one of three variants—namely, the Hum-mel-Dreyer method (1962), the vacancy peak method (Sebille, et al., 1979), and frontal analysis (Cooper and Wood, 1968)—is the traditional method of... 

H. Takahashi, H. Ogata, and Y. Seki, Binding interaction between enantiomers of disopyramide and mono-N-dealkyldisopyramide on plasma protein, Drug Melab. Dispos., 19 554 (1991). 

The half-life in the complete absence of renal function is increased by 70% or more. The reduced ability of plasma proteins to bind the drug (40), if this indeed occurs, will result in a greater proportion of unbound D-tubocurarine and therefore increased potency. 

Volland, C. Sun, H., Dammeyer, J. Benet, L.Z. Stereoselective Degradation of the Fenoprofen Acyl Glucuronide Enantiomers and Irreversible Binding to Plasma Protein, Drug Metab. Dispos. 19(6), 1080-1086 (1991). 

A) Drug B displaces warfarin from plasma proteins drug C displaces warfarin from tissue binding sites... 

Figure 9.27 Simplified scheme representing competition between binding to plasma proteins and binding to a drug s target receptor.

The acidic group in these compounds serves a major binding group (ionic binding) with plasma proteins. Thus, all NSAIDs are highly bound by plasma proteins (drug interactions). 

One of the plasma proteins which is mainly responsible for the plasma protein binding of drugs. Its level is known to be elevated in some pathological states, such as inflammation. 

Drug Interactions During Distribution Displacement from Plasma Protein Binding Sites... 

Lombardo F, Obach RS, Shalaeva MY and Gao F. Prediction of volume of distribution values in humans for neutral and basic drugs using physicochemical measurements and plasma protein binding data. J Med Chem 2002 45 2867-76. 

Kratochwil NA, Huber W, Muller F, Kansy M and Gerber PR. Predicting plasma protein binding of drugs a new approach. Biochem Pharmacol 2002 64 1355-74. 

The distribution of a drug in the body is largely driven by its physicochemical properties and in part for some compounds by the contribution of transporter proteins [17]. By using the Oie-Tozer equation and estimates for ionization (pfCj). plasma protein binding (PPB) and lipophilicity (log quite robust predictions for the volume of distribution at steady state (Vdss), often within 2-fold of the observed value, can be made [18]. 

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