d-penicillamine pharmacokinetics and pharmacodynamics in man

Joyce, David A.

doi:10.1016/0163-7258(89)90033-8

Cited by 26 publications

(13 citation statements)

References 169 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Penicillamine is well absorbed (40%-70%) from the gastrointestinal tract after oral administration (Joyce, 1989;Netter et al, 1987). Peak blood concentrations are attained in one to three hours.…”

Section: Pharmacokinetics Of Penicillaminementioning

confidence: 99%

“…Peak blood concentrations are attained in one to three hours. Absorption of penicil-lamine is reduced by 50% if given simultaneously with food, ferrous sulfate, or antacids (Joyce, 1989;Netter et al, 1987); therefore, penicillamine was given to patients between or after meals. Monitoring of penicillamine is technically diffi cult because of the presence of endogenous compounds with a thiol function and the presence of various metabolic byproducts of penicillamine (Netter et al, 1987).…”

Section: Pharmacokinetics Of Penicillaminementioning

confidence: 99%

See 1 more Smart Citation

Phase 2 trial of copper depletion and penicillamine as antiangiogenesis therapy of glioblastoma

Brem¹,

Grossman²,

Carson³

et al. 2005

Neuro-Oncology

108

View full text Add to dashboard Cite

Penicillamine is an oral agent used to treat intracerebral copper overload in Wilson's disease. Copper is a known regulator of angiogenesis; copper reduction inhibits experimental glioma growth and invasiveness. This study examined the feasibility, safety, and efficacy of creating a copper deficiency in human glioblastoma multiforme. Forty eligible patients with newly diagnosed glioblastoma multiforme began radiation therapy (6000 cGy in 30 fractions) in conjunction with a low-copper diet and escalating doses of penicillamine. Serum copper was measured at baseline and monthly. The primary end point of this study was overall survival compared to historical controls within the NABTT CNS Consortium database. The 25 males and 15 females who were enrolled had a median age of 54 years and a median Karnofsky performance status of 90. Surgical resection was performed in 83% of these patients. Normal serum copper levels at baseline (median, 130 microg/dl; range, 50-227 microg/dl) fell to the target range of <50 microg/dl (median, 42 microg/dl; range, 12-118 microg/dl) after two months. Penicillamine-induced hypocupremia was well tolerated for months. Drug-related myelosuppression, elevated liver function tests, and skin rash rapidly reversed with copper repletion. Median survival was 11.3 months, and progression-free survival was 7.1 months. Achievement of hypocupremia did not significantly increase survival. Although serum copper was effectively reduced by diet and penicillamine, this antiangiogenesis strategy did not improve survival in patients with glioblastoma multiforme.

show abstract

Section: Pharmacokinetics Of Penicillaminementioning

confidence: 99%

Section: Pharmacokinetics Of Penicillaminementioning

confidence: 99%

Phase 2 trial of copper depletion and penicillamine as antiangiogenesis therapy of glioblastoma

Brem¹,

Grossman²,

Carson³

et al. 2005

Neuro-Oncology

108

View full text Add to dashboard Cite

show abstract

“…More importantly, thiols play important roles in protecting biological systems from oxidative damage (2-4), e.g. GSH is the major intracellular low molecular weight thiol; dihydrolipoic acid is an endogenous dithiol with potent antioxidant properties (5,6); and other thiols such as penicillamine and N-acetylcysteine are used pharmacologically (7,8). Thiols such as cysteine and GSH have been reported to be substrates for horseradish peroxidase (9 -12).…”

mentioning

confidence: 99%

Protein Radical Formation during Lactoperoxidase-mediated Oxidation of the Suicide Substrate Glutathione

Guo

Detweiler

Mason

2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

A novel anti-5,5-dimethyl-1-pyrroline N-oxide (DMPO) polyclonal antiserum that specifically recognizes protein radical-derived DMPO nitrone adducts has been developed. In this study, we employed this new approach, which combines the specificity of spin trapping and the sensitivity of antigen-antibody interactions, to investigate protein radical formation from lactoperoxidase (LPO). When LPO reacted with GSH in the presence of DMPO, we detected an LPO radical-derived DMPO nitrone adduct using enzyme-linked immunosorbent assay and Western blotting. The formation of this nitrone adduct depended on the concentrations of GSH, LPO, and DMPO as well as pH values, and GSH could not be replaced by H 2 O 2 . The level of this nitrone adduct was decreased significantly by azide, catalase, ascorbate, iodide, thiocyanate, phenol, or nitrite. However, its formation was unaffected by chemical modification of free cysteine, tyrosine, and tryptophan residues on LPO. ESR spectra showed that a glutathiyl radical was formed from the LPO/GSH/DMPO system, but no protein radical adduct could be detected by ESR. Its formation was decreased by azide, catalase, ascorbate, iodide, or thiocyanate, whereas phenol or nitrite increased it. GSH caused marked changes in the spectrum of compound II of LPO, indicating that GSH binds to the heme of compound II, whereas phenol or nitrite prevented these changes and reduced compound II back to the native enzyme. GSH also dose-dependently inhibited the peroxidase activity of LPO as determined by measuring 2,2 -azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) oxidation. Taken together, these results demonstrate that the GSH-dependent LPO radical formation is mediated by the glutathiyl radical, possibly via the reaction of the glutathiyl radical with the heme of compound II to form a heme-centered radical trapped by DMPO.

show abstract

“…This then results in increased mobilization of copper from its protein ligand and tissues to the plasma, thereby, facilitating renal excretion. Unlike TM, a plasma surrogate for penicillamine activity has been difficult to identify thus far [29,30].…”

Section: Chemistry and Pharmacodynamicsmentioning

confidence: 99%

Copper chelation in cancer therapy using tetrathiomolybdate: an evolving paradigm

Khan

Merajver

2009

Expert Opinion on Investigational Drugs

View full text Add to dashboard Cite

Background: Tetrathiomolybdate (TM) is a novel anticancer and anti-angiogenic agent, which acts through copper chelation and NF-κB inhibition. Objective: This review summarizes the scientific rationale for the use of TM as an anticancer agent in human studies. Methods: A systematic review of the literature was conducted for the use of TM in cancer including preclinical, animal and human studies. The results of this search are summarized in this review. Results/conclusions: Copper chelation using TM has demonstrated efficacy in preclinical and animal models as an alternative and novel anti-angiogenic agent. Phase I and II clinical trials conducted in solid tumors using TM have demonstrated efficacy with favorable toxicity profile. The use of copper lowering as an anti-angiogenic strategy in the cancer chemopreventative setting remains to be investigated.

show abstract

d-penicillamine pharmacokinetics and pharmacodynamics in man

Cited by 26 publications

References 169 publications

Phase 2 trial of copper depletion and penicillamine as antiangiogenesis therapy of glioblastoma

Phase 2 trial of copper depletion and penicillamine as antiangiogenesis therapy of glioblastoma

Protein Radical Formation during Lactoperoxidase-mediated Oxidation of the Suicide Substrate Glutathione

Copper chelation in cancer therapy using tetrathiomolybdate: an evolving paradigm

Contact Info

Product

Resources

About