Advanced

Rapid exponential elimination of free prostate-specific antigen contrasts the slow, capacity-limited elimination of PSA complexed to alpha 1-antichymotrypsin from serum

Björk, Thomas LU ; Ljungberg, Bengt LU ; Piironen, Timo; Abrahamsson, Per-Anders LU ; Pettersson, Kim; Cockett, Abraham T and Lilja, Hans LU (1998) In Urology 51(1). p.57-62
Abstract
OBJECTIVES: To study the rates of elimination of total prostate-specific antigen (PSA-T), free PSA (PSA-F), and PSA complexed to alpha 1-antichymotrypsin (PSA-ACT) from blood after radical retropubic prostatectomy (RRP). METHODS: We obtained venous blood from 10 patients with prostate cancer who were undergoing RRP. We analyzed PSA-F and PSA-ACT and equimolar detection of both of these forms together (PSA-T) by using immunofluorometric assays. An attempt was made to fit the serum concentrations of PSA-F, PSA-ACT, and PSA-T for each patient to exponential curves by applying one- and two-compartment models for pharmacokinetic analysis. RESULTS: Manipulation of the prostate during RRP resulted in a 3- to 28-fold increase in PSA-F... (More)
OBJECTIVES: To study the rates of elimination of total prostate-specific antigen (PSA-T), free PSA (PSA-F), and PSA complexed to alpha 1-antichymotrypsin (PSA-ACT) from blood after radical retropubic prostatectomy (RRP). METHODS: We obtained venous blood from 10 patients with prostate cancer who were undergoing RRP. We analyzed PSA-F and PSA-ACT and equimolar detection of both of these forms together (PSA-T) by using immunofluorometric assays. An attempt was made to fit the serum concentrations of PSA-F, PSA-ACT, and PSA-T for each patient to exponential curves by applying one- and two-compartment models for pharmacokinetic analysis. RESULTS: Manipulation of the prostate during RRP resulted in a 3- to 28-fold increase in PSA-F concentrations in serum. Removal of the prostate resulted in a rapid, biexponential elimination of PSA-F from serum, corresponding to a mean initial (alpha) half-life of 0.81 hours and a mean terminal (beta) half-life of 13.9 hours. Serum PSA-ACT concentrations decreased by 20% to 40% immediately after removal of the gland; the elimination after surgery was slow and nonexponential, corresponding to a mean rate of 0.8 ng/mL/day. The elimination of PSA-T reflects a combination of the elimination patterns for PSA-F and PSA-ACT. CONCLUSIONS: The main proportion of PSA-F is rapidly eliminated from serum, possibly by glomerular filtration. PSA-F released during surgery did not form complexes with ACT, as suggested by the lack of PSA-ACT elevation in serum. The size (approximately 90 kDa) and the extensive in vitro stability of the PSA-ACT complex prevents renal clearance. The nonexponential elimination of the PSA-ACT complex is evidence of a capacity-limited process (e.g., metabolic transformation). (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Urology
volume
51
issue
1
pages
57 - 62
publisher
Elsevier
external identifiers
  • pmid:9457289
  • scopus:0031891632
ISSN
1527-9995
DOI
10.1016/S0090-4295(97)00572-4
language
English
LU publication?
yes
id
7c1476ea-97e6-4c78-b68b-0be4bb3f3489 (old id 1112943)
date added to LUP
2008-07-11 15:29:00
date last changed
2017-01-01 05:15:53
@article{7c1476ea-97e6-4c78-b68b-0be4bb3f3489,
  abstract     = {OBJECTIVES: To study the rates of elimination of total prostate-specific antigen (PSA-T), free PSA (PSA-F), and PSA complexed to alpha 1-antichymotrypsin (PSA-ACT) from blood after radical retropubic prostatectomy (RRP). METHODS: We obtained venous blood from 10 patients with prostate cancer who were undergoing RRP. We analyzed PSA-F and PSA-ACT and equimolar detection of both of these forms together (PSA-T) by using immunofluorometric assays. An attempt was made to fit the serum concentrations of PSA-F, PSA-ACT, and PSA-T for each patient to exponential curves by applying one- and two-compartment models for pharmacokinetic analysis. RESULTS: Manipulation of the prostate during RRP resulted in a 3- to 28-fold increase in PSA-F concentrations in serum. Removal of the prostate resulted in a rapid, biexponential elimination of PSA-F from serum, corresponding to a mean initial (alpha) half-life of 0.81 hours and a mean terminal (beta) half-life of 13.9 hours. Serum PSA-ACT concentrations decreased by 20% to 40% immediately after removal of the gland; the elimination after surgery was slow and nonexponential, corresponding to a mean rate of 0.8 ng/mL/day. The elimination of PSA-T reflects a combination of the elimination patterns for PSA-F and PSA-ACT. CONCLUSIONS: The main proportion of PSA-F is rapidly eliminated from serum, possibly by glomerular filtration. PSA-F released during surgery did not form complexes with ACT, as suggested by the lack of PSA-ACT elevation in serum. The size (approximately 90 kDa) and the extensive in vitro stability of the PSA-ACT complex prevents renal clearance. The nonexponential elimination of the PSA-ACT complex is evidence of a capacity-limited process (e.g., metabolic transformation).},
  author       = {Björk, Thomas and Ljungberg, Bengt and Piironen, Timo and Abrahamsson, Per-Anders and Pettersson, Kim and Cockett, Abraham T and Lilja, Hans},
  issn         = {1527-9995},
  language     = {eng},
  number       = {1},
  pages        = {57--62},
  publisher    = {Elsevier},
  series       = {Urology},
  title        = {Rapid exponential elimination of free prostate-specific antigen contrasts the slow, capacity-limited elimination of PSA complexed to alpha 1-antichymotrypsin from serum},
  url          = {http://dx.doi.org/10.1016/S0090-4295(97)00572-4},
  volume       = {51},
  year         = {1998},
}