Propranolol plasma protein binding

Verbeeck RK, Cardinal J (1985) Plasma protein binding of salicylic acid, phenytoin, chlorpromazine, propranolol and pethidine using equilibrium dialysis and ultracentrifugation. Arzneimittelforschung 35 903... 

H. Takahashi, H. Ogata, S. Kanno, and H. Takeuchi, Plasma protein binding of propranolol enantiomers as a major determinant of their stereoselective tissue distribution in rats, J. Pharmacd. Exp. Then, 252 272 (1990). 

One clinically relevant observation that arises from this relationship is that the apparent volume of distribution for a drug is dependent upon the extent of plasma protein binding. Hence, drugs with more extensive plasma protein binding, like tolbutamide (95% bound), will have a lower volume of distribution than expected based on its lipophilicity (log P= 2.34). This influence of plasma protein binding has been shown to contribute to the intersubject variability in the volume of distribution for a number of drugs (e.g., propranolol in liver disease Branch et al., 1976). 

A a Eh X 0 a e Eh P) t=L Use with caution in patients over 50 years oid with kidney or liver faiiure. PO/IV/IM. Little plasma protein binding, little metabolism. Cimetidine increases serum concentrations of many drugs (oral anticoagulants, theophylline, lidocaine, phenytoin, benzodiazepines, nifedipine, propranolol) by inhibiting liver P450 enzymes. May inhibit renal tubular secretion of procainamide. ... 

Age and gender do not appear to play a substantial role in the plasma protein binding of propranolol enantiomers (Table 2). A modestly lower unbound fraction of (-)-propranolol in females (10.9%, Table 2) compared with males (12.8%, Table 2) reported in one study [21] was not observed in a subsequent study [22] which reported an unbound fraction of 9.1 and 9.2 in men and women, respectively (Table 2). 

Takahashi, H. Ogata, El. Plasma protein binding and blood cell distribution of propranolol enantiomers in rats. Biochem. Pharmacol. 1990, 39, 1495-1498. 

In a total volume of 300 pi, 50pl reticulocyte membranes in phosphate buffer (500 pg protein) were incubated for 60 min at 25°C with 50 pi (30 nCi) of (-)-3H-CGP-12177, 180 pi of plasma and 20pl of 310 mOsm sodium phosphate buffer (pH 7.4). Standard curves were run for each rabbit separately in order to avoid errors due to possible differences in protein binding. To generate the standard curves, blank plasma was used and incubated in the presence of 1-20 nM timolol. For the determination of non-specific binding, incubation in a 10-5 M propranolol solution was used. 

The use of vacutainer tubes and heparin was shown to alter the determination of protein binding. Heparin was shown to decrease the plasma binding of certain drugs including phenytoin, propranolol, lidocaine, diazepam, quinidine, and verapamil. This is also an in vitro artifact attributable to continued ex vivo activity of the lipoprotein lipase enzyme and accumulation of fatty acids in the blood collection tube. 

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