ANTI-PHENCYCLIDINE MONOCLONAL FAB FRAGMENTS MARKEDLY ALTER PHENCYCLIDINE PHARMACOKINETICS IN RATS

被引:0
|
作者
VALENTINE, JL
ARNOLD, LW
OWENS, SM
机构
[1] UNIV ARKANSAS MED SCI HOSP,COLL MED,DEPT PHARMACOL & TOXICOL,LITTLE ROCK,AR 72205
[2] UNIV N CAROLINA,SCH MED,DEPT MICROBIOL & IMMUNOL,CHAPEL HILL,NC 27599
来源
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS | 1994年 / 269卷 / 03期
关键词
D O I
暂无
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The purpose of these studies was to explore the use of phencyclidine (PCP)-specific high affinity antibodies as a possible treatment for phencyclidine toxicity. High affinity (K-d = 1.8 nM) anti-POP monoclonal Fab fragments were purified from papain digested anti-POP immunoglobulin produced in mouse ascites. Control animals (n = 5) received an i.v. bolus dose of 1 mg/kg of PCP, along with a tracer dose of 250 mu Cl of [H-3]PCP. Fab-treated rats (n = 5) also received this PCP dose. but at 2 hr after dosing (when PCP distribution was complete) they received an equimolar dose of anti-PCP Fab (50 mg). Within 5 min after the anti-POP Fab administration, serum [H-3]PCP concentrations increased approximately 60- to 100-fold. Fab treatment caused the [H-3]PCP volume of distribution at steady state to decrease from 12.6 +/- 3.0 liters/kg (mean +/- S.D.) in control animals to 0.6 +/- 0.2 liters/kg in the Fab-treated animals (about 5% of control values). Systemic clearance changed from 66.3 +/- 16.9 to 6.8 +/- 2.8 ml/min/kg (about 10% of control values). Because both volume of distribution and systemic clearance decreased to a similar degree, the terminal elimination half-life did not change significantly (3.9 hr in controls vs. 4.9 hr in treated animals, harmonic means). Renal clearance decreased from 1.8 +/- 0.6 to 0.62 +/- 0.17 ml/min/kg after Fab treatment. The anti-POP Fab caused the percentage of PCP recovered in urine to increase from 2.5 +/- 0.5 to 10.3 +/- 4.7%. The cumulative percentage of total radioactivity ([H-3]PCP plus H-3-metabolites) in the urine was not altered by the Fab treatment. Except for T-1/2 lambda z and total radioactivity in the urine, all pharmacokinetic parameters after anti-POP Fab treatment were significantly different from controls (Student's t test, P <.05). These dramatic changes in PCP pharmacokinetics suggest anti-POP Fab fragments could decrease PCP toxicity in overdose situations.
引用
收藏
页码:1079 / 1085
页数:7
相关论文
共 50 条
  • [31] Safety, inhibition of platelet aggregation and pharmacokinetics of Fab'2 fragments of the anti-glycoprotein llb-llla monoclonal antibody framon in high-risk coronary angioplasty
    Pevzner, D
    Ruda, M
    Mazurov, A
    JOURNAL OF HYPERTENSION, 2003, 21 : S334 - S334
  • [32] In vivo stability and metabolism of 99Tcm-labelled anti-CD4 monoclonal antibodies and Fab′ fragments
    Kinne, RW
    Schemer, K
    Behr, T
    Sharkey, RM
    Palombo-Kinne, E
    Emmrich, F
    Goldenberg, DM
    Wolf, F
    Becker, W
    NUCLEAR MEDICINE COMMUNICATIONS, 1999, 20 (01) : 67 - 75
  • [33] Use of anti-(+)-methamphetamine monoclonal antibody to significantly alter (+)-methamphetamine and (+)-amphetamine disposition in rats
    Laurenzana, EM
    Byrnes-Blake, KA
    Milesi-Hallé, A
    Gentry, WB
    Williams, DK
    Owens, SM
    DRUG METABOLISM AND DISPOSITION, 2003, 31 (11) : 1320 - 1326
  • [34] Effect of a Humanized Anti-Cocaine Monoclonal Antibody on the Pharmacokinetics of Cocaine in Rats and Mice
    Gooden, Felicia C. T.
    Tabet, Michael R.
    Bartley, Erin L.
    Ball, William J.
    Norman, Andrew B.
    FASEB JOURNAL, 2013, 27
  • [35] BIOLOGICAL ACTION OF MONOCLONAL ANTI-HUMAN INSULIN-RECEPTOR ANTIBODIES IS MIMICKED BY CROSS-LINKED FAB FRAGMENTS
    WELLS, A
    SOOS, M
    SIDDLE, K
    TAYLOR, R
    DIABETOLOGIA, 1989, 32 (07) : A556 - A556
  • [36] SUPPRESSION OF COLLAGEN-INDUCED ARTHRITIS IN MICE BY FAB FRAGMENTS OF ARTHRITOGENIC ANTI-TYPE II COLLAGEN MONOCLONAL ANTIBODIES
    Yoshino, S.
    ANNALS OF THE RHEUMATIC DISEASES, 2015, 74 : 938 - 938
  • [37] From agonist to antagonist:: Fab fragments of an "agonist-like" monoclonal anti-β2 adrenoceptor antibody behave as antagonists
    Mijares, A
    Lebesgue, D
    Wallukat, G
    Hoebeke, J
    HYPERTENSION, 1999, 34 (04) : 713 - 713
  • [38] Antigen-specific regulation of asthmatic responses in mice by intratracheal exposure to anti-ovalbumin monoclonal antibody Fab fragments
    Yoshino, S.
    Mizutani, N.
    Ammori, Y.
    Torii, H.
    ALLERGY, 2013, 68 : 237 - 237
  • [39] Characterization of human anti-heat shock protein 60 monoclonal autoantibody Fab fragments in atherosclerosis: Genetic and functional analysis
    Jang, Eun-Jung
    Jung, Kui-Yea
    Hwang, Eunjoo
    Jang, Young-Ju
    MOLECULAR IMMUNOLOGY, 2013, 54 (3-4) : 338 - 346
  • [40] From agonist to antagonist:: Fab fragments of an agonist-like monoclonal anti-β2-adrenoceptor antibody behave as antagonists
    Mijares, A
    Lebesgue, D
    Wallukat, G
    Hoebeke, J
    MOLECULAR PHARMACOLOGY, 2000, 58 (02) : 373 - 379