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Abstract

Phencyclidine blood protein binding: influence of protein, pH and species.

S M Owens, M Mayersohn and J R Woodworth
Journal of Pharmacology and Experimental Therapeutics September 1983, 226 (3) 656-660;
S M Owens
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M Mayersohn
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J R Woodworth
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Abstract

We studied the influence of protein, pH and species on phencyclidine (PCP) protein binding. PCP binding to dog serum was unaffected by high concentrations of PCP and metabolites. The percentage of unbound PCP in pooled human serum and plasma specimens and pooled dog serum specimens was (mean +/- S.D.): 48.3 +/- 2.5; 42.5 +/- 1.8; and 43.3 +/- 1.9%, respectively. The percentage of unbound PCP in human serum albumin (HSA), 81.2 +/- 2.0%, was constant over the physiological HSA concentration range (3.5-5.5 g/dl). The binding of PCP to alpha 1-acid glycoprotein (alpha 1-AGP) increased with increasing alpha 1-AGP concentration (50-200 mg/dl). The binding to HSA or alpha 1-AGP separately did not account for the binding found in whole serum or plasma specimens. However, when a constant concentration of HSA (4.5 g/dl) was added to varying concentrations of alpha 1-AGP, the PCP binding increased dramatically and was similar to the binding found in human serum specimens. The association constant in the presence of both proteins (7.72 X 10(4) M-1) was 4.4 times greater than the association constant for alpha 1-AGP alone (1.74 X 10(4) M-1). This suggested an interaction between the proteins which resulted in enhanced PCP binding. The percentage of unbound PCP increased with decreasing pH in both dog serum and human serum specimens. This change could have possible effects on PCP distribution and elimination. The PCP blood to plasma ratio was 0.94 in pooled human heparinized blood and 1.25 in pooled dog heparinized blood. Neither species showed PCP concentration-dependent partitioning.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 226, Issue 3
1 Sep 1983
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Abstract

Phencyclidine blood protein binding: influence of protein, pH and species.

S M Owens, M Mayersohn and J R Woodworth
Journal of Pharmacology and Experimental Therapeutics September 1, 1983, 226 (3) 656-660;

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Abstract

Phencyclidine blood protein binding: influence of protein, pH and species.

S M Owens, M Mayersohn and J R Woodworth
Journal of Pharmacology and Experimental Therapeutics September 1, 1983, 226 (3) 656-660;
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