Plasma protein binding of phencyclidine

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Abstract
In healthy male subjects (12) phencyclidine (PCP) [a widely abused drug] free fraction was 22.0 .+-. 2.8% (.hivin.x [mean] .+-. SD). In male patients with mild to moderate alcoholic liver disease (16) free fraction (23.0 .+-. 3.4%) was of the same order as in healthy subjects although age and the concentrations of albumin, bilirubin and high-density lipoproteins were different (P < 0.05). Free fraction (76.2 .+-. 0.06%) in fatty acid free human serum albumin (HSA, 4.4 g/dl) was far greater than in plasma. Both the increased binding of PCP in plasma over HSA and the lack of a difference in PCP binding between normals and patients was associated with .alpha.1-acid glycoprotein (.alpha.1-AGP). This protein is an acute-phase reactant that binds cationic drugs and rises nonspecifically in a variety of diseases. Free fraction of PCP in .alpha.1-AGP (75 mg/dl) was 36.4 .+-. 1.7%. Half of the variance in PCP binding can be accounted for (r = 0.67, P < 0.01) from percentage of free PCP = 39.24 - 2.18 (albumin) - 0.094 (.alpha.1-AGP). Male rats (14, wt = 251 .+-. 7 g) were alternatively assigned to pretreatment with either saline or .alpha.1-AGP (11.6 mg) by cardiac puncture. PCP brain concentrations were reduced (11%, P < 0.05) in the protein-treated group 5 min after cardiac 3H-PCP (0.17 mg) administration, demonstrating that increased plasma protein binding can reduce free drug concentration during the distribution phase and, thereby, the rate and extent of drug distribution.