D-penicillamine Group Research Articles

The Effects of Succimer and Penicillamine on Acute Lead Poisoning Patients

Background: Lead poisoning was on the rise in recent years. There exists a lack of easy access to some of the main chelator drugs in developing countries. Thus, this study aimed to explore the comparative effects of Succimer and D-Penicillamine on acute lead poisoning patients from 2013 to 2018. Methods: This descriptive study was conducted in the Clinical Toxicology Department of Khorshid Hospital in Isfahan City, Iran. Adult patients with acute lead poisoning were included in the study. Patients in the 3 treatment groups of D-Penicillamine, D-Penicillamine with succimer, and succimer were compared concerning demographic characteristics as well as clinical and laboratory findings at admission time and two weeks later. Results: In total, 163 patients were evaluated in this research. There was no significant difference between the treatment groups respecting improvement in clinical symptoms. The mean blood lead levels during hospitalization and two weeks after the treatment did not significantly differ between the three groups; however, there was a significant reduction in all study groups after two weeks of treatment (P<0.05). The mean white blood cell count was significantly lower only in the D-Penicillamine group two weeks after hospitalization (P<0.05). In the D-Penicillamine group, the mean platelet, hematocrit, and hemoglobin levels were significantly lower two weeks after hospitalization, although within the healthy range. Conclusion: D-Penicillamine may be an acceptable chelator drug for treating patients with acute lead poisoning, especially in communities without access to drugs, like succimer.

Comparison of Therapeutic Effects of Garlic and d‐Penicillamine in Patients with Chronic Occupational Lead Poisoning

Previous studies on animals have revealed that garlic (Allium sativum) is effective in reducing blood and tissue lead concentrations. The aim of this study was to investigate therapeutic effects of garlic and compare it with d-penicillamine in patients with chronic lead poisoning. After coordination and obtaining informed consent, clinical examinations and blood lead concentration (BLC) of 117 workers at a car battery industry were investigated. BLC was determined by heated graphite atomization technique of an atomic absorption spectrometer. The workers were randomly assigned into two groups of garlic (1200 μg allicin, three times daily) and d-penicillamine (250 mg, three times daily) and treated for 4 weeks. BLC was determined again 10days post-treatment. Clinical signs and symptoms of lead poisoning were also investigated and compared with the initial findings. Clinical improvement was significant in a number of clinical manifestations including irritability (p = 0.031), headache (p = 0.028), decreased deep tendon reflex (p=0.019) and mean systolic blood pressure (0.021) after treatment with garlic, but not d-penicillamine. BLCs were reduced significantly (p=0.002 and p=0.025) from 426.32±185.128 to 347.34±121.056 μg/L and from 417.47±192.54 to 315.76±140.00μg/L in the garlic and d-penicillamine groups, respectively, with no significant difference (p=0.892) between the two groups. The frequency of side effects was significantly (p=0.023) higher in d-penicillamine than in the garlic group. Thus, garlic seems safer clinically and as effective as d-penicillamine. Therefore, garlic can be recommended for the treatment of mild-to-moderate lead poisoning.

The effects of D-penicillamine on a murine model of oxygen-induced retinopathy

To determine the effect of intraperitoneal and intravitreal D-penicillamine (DPA) on retinal neovascularization in a murine model of oxygen-induced retinopathy. On postnatal day 7, 16 mice were injected intraperitoneally with 300 mg/kg/day DPA for 3 days followed by 50 mg/kg/day for 7 days. A different group of 7 mice were injected intraperitoneally with 600 mg/kg/day DPA for 3 days followed by 100 mg/kg/day for 7 days. A third group of 14 mice were injected with 1,500 mg/kg/day DPA for 2 days; a control cohort of 17 mice received intraperitoneal phosphate-buffered saline (PBS). An additional 15 mice underwent intravitreal injection of 1 μL of 100 mg/mL DPA in the right eye and 1 μL PBS intravitreally in the left eye as a control. All groups were placed in a 75% oxygen chamber for 7 days then room air for 3 days before being sacrificed and enucleated. The retinas were stained and flat-mounted to determine the severity of retinal neovascularization by quantifying neovascular buds. After intraperitoneal injection, the mean number of glomeruli and tubules was similar in the DPA and PBS groups (P = 1.0), regardless of DPA dosage. The dosage of 1,500 mg/kg/day proved to be uniformly lethal. After intravitreal injections, the mean number of glomeruli (P= 0.16) and tubules (P = 0.7) were similar in the DPA and PBS groups. Neither intraperitoneal nor intravitreal injection of DPA inhibits retinal neovascularization in a murine model of oxygen-induced retinopathy.

Penicillamine for rheumatoid arthritis.

To estimate the short-term effects of D-penicillamine for the treatment of rheumatoid arthritis (RA). We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register, Medline up to and including December 1998 and Embase from 1988-1998. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search. All randomized controlled trials and controlled clinical trials comparing D-penicillamine against placebo in patients with rheumatoid arthritis. The methodological quality of the trials was assessed independently by two reviewers (CS, EB) and checked by a third (MS) using a validated quality assessment tool. Rheumatoid arthritis outcome measures were extracted from the publications for the six-month endpoint and stratified according to D-penicillamine dosages: low (<500mg/day), moderate (500 to <1000mg/day) and high (1000 mg/day or greater). Data was abstracted by one reviewer and checked by a second (CS, MS). The pooled analysis was performed using the standardized mean difference for joint counts, pain and global assessments. The weighted mean difference was used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals and adverse reactions. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout, since no statistical heterogeneity was found. Six trials were identified, with 425 patients randomized to D-penacillamine and 258 to placebo. A statistically significant benefit was observed for D-penicillamine when compared to placebo for all three-dose ranges and for most outcome measures including: tender joint counts, pain, physician's global assessments and ESR. The standardized weighted mean differences between treatment and placebo in moderate doses were -0. 51 [95% CI -0.88, -0.14] for tender joint counts, -0.56 (95% CI -0. 87, -0.26) for pain and -0.97 (95% CI -1.25, -0.70) for global assessment. The difference for ESR was -10.6 mm/hr. Similar results were observed for the higher dose group. Total withdrawals were significantly higher in the moderate and high dosage D-penicillamine groups (OR=1.63 and 2.13 respectively), mostly due to increased adverse reactions (OR = 2.60 and 4.95 respectively), including renal and hematological abnormalities. D-penicillamine appears to have a clinically and statistically significant benefit on the disease activity of patients with rheumatoid arthritis. Its efficacy appears to be similar to that of other disease modifying anti-rheumatic drugs (DMARDs), but with a significantly higher toxicity. Its effects on long-term functional status and radiological progression are not clear from this review.

D-penicillamine inhibits the action of reactive oxygen species in the pig pulmonary circulation.

Oxygen radicals produced by the hypoxanthine-xanthine oxidase (Hyp-XO) system potently constrict the pulmonary circulation of pigs. D-penicillamine (DPA) is thought to be a free radical scavenger. In the present work we have studied if DPA may influence the vasoactive action of Hyp-XO in pig lungs. Further, we have measured how this drug influences the output of cyclooxygenase and lipoxygenase products from the left atrium in pigs infused with XO into the pulmonary circulation. Twelve young pigs were divided into two groups. Group 1, the XO group, was infused 1 U/kg XO into right atrium. Group 2, the DPA group, was pretreated with DPA, 100 mg/kg intravenously before XO infusion as in group 1. Pulmonary artery pressure, left atrial pressure, pulmonary artery blood flow and systemic blood flow and pressure were recorded continuously. Plasma tromboxane B2 and prostaglandin (6-keto-PGF1 alpha) were determined with a radioimmunoassay method. Cysteinyl containing leukotrienes LTC4, LTD4, and LTE4, were measured together by RIA analyses of plasma samples, using a monoclonal antibody. There was a significant parallel decrease in paO2 and saO2 during the 130 minutes duration of the experiments in both groups without differences between the groups. Pulmonary vascular pressure and resistance increased sharply with a peak found after 25 minutes in the XO group. DPA attenuated the hemodynamic response. DPA inhibited the XO induced pulmonary blood pressure changes with 80% and inhibited the increase in pulmonary vascular resistance 68%. Plasma TXB2 increased two folds in the XO group reaching a maximum after 40 minutes, this effect was completely inhibited by DPA (92% inhibition). DPA also inhibited the XO induced increase in 6-keto-PGF1 alpha, however, not as efficient as with TXB2 (40% inhibition). Plasma cysteinyl leukotrienes increased after XO infusion reaching a peak at 20 minutes. DPA completely abolished this effect (100% inhibition). The study demonstrates that DPA attenuates or even abolishes the hemodynamic effects of XO on the pulmonary circulation in pigs. It seems that DPA inhibits the production of both lipoxygenase and cyclooxygenase products per se, and it is tempting to speculate that the observed DPA effect is caused by its action as an oxygen radical scavenger. It is further speculated that the vasoconstricting effect of XO is due to the fact that oxygen radicals may inactivate nitric oxide (NO), and that DPA stabilizes NO so it more efficiently possess its vasorelaxant activity. We conclude that DPA is an extremely potent inhibitor of XO induced pulmonary vascular effects. The mechanism of action is not fully understood, although its action as an oxygen radical scavenger may explain part of it.

Temporal patterns of response to D-penicillamine, hydroxychloroquine, and placebo in juvenile rheumatoid arthritis patients.

We calculated the time required for therapeutic benefit to become apparent following initiation of treatment with D-penicillamine (DP), hydroxychloroquine (HCQ), or placebo (each administered concomitantly with a nonsteroidal antiinflammatory drug) using data from a double-blind, randomized 12-month trial in 162 patients with juvenile rheumatoid arthritis. Using previously published criteria to classify the outcome, we found that 60% of the HCQ group, 46% of the DP group, and 39% of the placebo group responded favorably after 12 months of therapy. Data from examinations between the initial and final assessments were used to determine when the response first occurred. Approximately 50% of all patients who showed improvement at 12 months had already done so by 2 months. After 6 months, 96% of the DP group, 88% of the HCQ group, and 85% of the placebo group responders had met the criteria for response. The average time until response was attained was 105 days for the DP group, 129 days for the HCQ group, and 140 days for the placebo group. Our results indicate that a favorable response to these slow-acting antirheumatic drugs is unlikely if improvement has not occurred within the first 6 months of therapy.

Auranofin or D-Penicillamine in the Treatment of Rheumatoid Arthritis

Ninety patients were entered into a randomized, controlled, double-blind trial lasting 12 months to compare auranofin (6 mg/d), and D-penicillamine (250 mg/d for 4 weeks, 500 mg/d for 4 weeks, then 750 mg/d thereafter) in the treatment of rheumatoid arthritis. Most patients in both groups completed the trial with significant improvement in all quantitative measures of efficacy. Patients treated with D-penicillamine were more likely to have "important improvement" in physician global assessment, swollen joint count, and score and grip strength. The overall frequency of side effects was similar between the two groups; however, more patients were withdrawn for adverse effects from the D-penicillamine group, and proteinuria (greater than or equal to 2+) and thrombocytopenia (less than 100 000 mm3) occurred significantly more frequently with D-penicillamine than auranofin (p = 0.028). These results suggest that in the dosage regimen used, auranofin is safer than D-penicillamine but that D-penicillamine tends to show greater clinical effectiveness in patients with rheumatoid arthritis.

Teratogenesis and low copper status resulting from D-penicillamine in rats.

The teratogenicity of D-penicillamine was studied using the Sprague-Dawley rat. Fetuses from rats fed diets containing 0.83% D-penicillamine during pregnancy had a high incidence of malformations. Maternal and fetal tissue copper levels were significantly lower in the D-penicillamine group than in controls, suggesting that the teratogenicity of the drug may be due in part to the induction of copper deficiency by its chelating properties.

Effects of Penicillamine and Hydroxyquinoline on Absorption of Orally Ingested 65Zinc in the Rat

The influence of high doses of 2 chelating agents, D-penicillamine and iodochlorohydroxyquin, on the metabolism of orally ingested 65 Zn was studied on rats by means of whole body counting assay technique. Both drugs were found to increase zinc absorption in a dose-dependent way to values significantly above those of the untreated control group. At identical doses D-penicillamine had a significantly stronger enhancing effect than the 8-hydroxyquinoline derivate, except for the highest dosage which was 100 mg daily. The turnover of the absorbed 65Zn fraction was followed during the time of observation which was 11 days. The elimination rate was practically identical in all experimental groups, except for the 100 mg D-penicillamine group in which the biological half-life of 65Zn was significantly decreased as compared to the control group.

A CONTROLLED TRIAL OF D-PENICILLAMINE THERAPY IN PRIMARY BILIARY CIRRHOSIS

D-penicillamine, 900 mg daily, was used in a randomised controlled trial for treatment of patients with primary biliary cirrhosis. 19 patients received D-penicillamine and 13 received placebo. The two groups were similar in age, duration of illness, liver function tests, and liver histology. Before entry into the trial liver-copper concentration was raised in 25 of the 27 patients in whom it was measured. After three months patients taking D-penicillamine showed a significant reduction in serum-aspartate-transaminase concentrations compared with the placebo group, and this reduction seemed to be sustained. In the 4 patients on D-penicillamine for a year, a second liver biopsy showed that mean liver-copper concentration fell from 310±128 (S.E.M.) to 84±36 μg/g dry liver, compared with a reduction from 511±169 to 454±128 in the 7 patients in the placebo group in whom serial liver-copper measurements were available. Liver histology demonstrated a comparative improvement in cholestasis in pa tients on penicillamine, but the degree of inflammation, necrosis, and the histological stage of disease remained similar in both groups. In 5 of the 19 patients in the D-penicillamine group the drug was discontinued because of side-effects. D-penicillamine seems to be a promising treatment for patients with primary biliary cirrhosis. It may produce its effect by reducing liver-copper concentration.

Controlled trial of synthetic D-penicillamine and prednisone in maintenance therapy for active chronic hepatitis.

In view of promising, but uncontrolled, reports of the use of D-penicillamine in active chronic hepatitis, a randomised, prospective, controlled trial of this drug against prednisone was carried out. Of the 35 patients entered, 18 received D-penicillamine (increasing to 1-2 g daily) and 17 prednisone (15 mg daily). In all patients the disease had already been brought under biochemical control with corticosteroids. During the first year of the trial, the treatment of nine patients in the D-penicillamine group was discontinued (two because of lack of disease control and seven because of side-effects) compared with six patients in the prednisone group (four because of lack of disease control, one because of side-effects, and one because of the development of carcinomatosis. Detailed statistical analysis of the liver function tests in the patients remaining in the trial at the end of the year showed no significant differences. D-penicillamine is associated with a higher frequency of side-effects than is prednisone. However, in some patients it is as satisfactory as prednisone in keeping the disease under control.