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Plasma protein binding of phencyclidine
Author(s) -
Giles H G,
Corrigall W A,
Khouw V,
Sellers E M
Publication year - 1982
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1982.12
Subject(s) - free fraction , phencyclidine , albumin , chemistry , medicine , blood proteins , endocrinology , human serum albumin , distribution (mathematics) , plasma protein binding , pharmacology , bilirubin , biochemistry , receptor , nmda receptor , mathematics , mathematical analysis
In healthy male subjects (n = 12) phencyclidine (PCP) free fraction was 22.0 ± 2.8% ( x ± SD). In male patients with mild to moderate alcoholic liver disease (n = 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 gm/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 aacid glycoprotein (α 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 α 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 (α 1 ‐AGP). Male rats (n = 14, weight = 251 ± 7 gm) were alternatively assigned to pretreatment with either saline or α 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 3 H‐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. Clinical Pharmacology and Therapeutics (1982) 31 , 77–82; doi: 10.1038/clpt.1982.12