Penicillamine Foods

There is an increased risk of toxicity of MTX when administered with the NSAIDs, salicylates, oral antidiabetic drugs, phenytoin, tetracycline, and probenecid. There is an additive bone marrow depressant effect when administered with other drug known to depress the bone marrow or with radiation therapy. There is an increased risk for nephrotoxicity when MTX is administered with other drug that cause nephrotoxicity. When penicillamine is administered with digoxin, decreased blood levels of digoxin may occur. There is a decreased absorption of penicillamine when the dmg is administered with food, iron preparations, and antacids. 

Penicillamine is well absorbed (40-70%) from the gastro-intestinal tract and, therefore, has a decided advantage over many chelating agents. Food, antacids, and iron reduce its absorption, so it should be taken on an empty stomach. Preferably, the... 

It has been found that the absorption of penicillamine is decreased by 52% when taken with food. 

Give penicillamine on an empty stomach at least 1 hour before meals or 2 hours after meals and at least 1 hour apart from any other drug, food, or milk. 

Drugs that may affect penicillamine include gold therapy, antimalarial or cytotoxic drugs, iron salts, antacids, and food. 

Milk and dairy foods decrease the absorption of some tetracyclines (doxycycline and minocycline are not affected), some quinolone antibiotics (absorption of ciprofloxacin and norfloxacin is decreased but ofloxacin is not affected), penicillamine and alendronate. Large volumes of milk can reduce the ulcer-healing properties of bismuth tripotassium dicitratobismuthate (bismuth chelate),... 

Hepatolenticular degeneration (Wilson s disease) is caused by a genetic failure to eliminate copper absorbed from food so that it accumulates in the liver, brain, cornea and kidneys. Chelating copper in the gut with penicillamine (p. 293) or trientine can establish a negative copper balance (with some clinical improvement if treatment is started early). The patients may also develop cirrhosis, and the best treatment for both may be orthotopic liver transplantation. 

Osman MA, Patel RB, Schnna A, Snndstrom WR, Welling PG. Reduction in oral penicillamine absorption by food, antacid, and ferrous sulfate. CUn Pharmacol Ther 1983 33(4) 465-70. 

Patents have issued for the use of amino-acid complexes [253], copper-metallothioneins [254], compositions of copper compounds mixed with fatty acids [253], copper complexes of D-penicillamine, alkylcysteines [256, 257] and copper complexes offatty acids alone or mixed with metallic copper [258]. Compositions of copper compounds mixed with fatty acids were also claimed to be useful in the treatment of other inflammatory disorders, including cardiovascular and thrombotic disorders, menstrual cycle disorders, diabetes, endometriosis, nutritional deficiencies and malignancies [255]. Scheinberg has also obtained a Food and Drug Administration approved Investigational New Drug application for the treatment of RA with the mixed-valence copper penicillamine complex (personal communication). Preparations of Cu(II)-(oleate) are currently being sold in Europe for topical treatment of RA and other inflammatory disorders under the trade names of Kupfer and Kupfer Forte, which contains fine particles of metallic copper [258]. 

Penicillamine is well absorbed (40-70%) from the GI tract and therefore has a decided advantage over many other chelating agents. Food, antacids, and iron reduce its absorption. Peak concentrations in blood are obtained 1—3 hours after administration. Unlike cysteine, its nonmethylated parent compound, penicillamine, is somewhat resistant to attack by cysteine desulfhydrase or L-amino acid oxidase and is relatively stable in vivo. Hepatic biotransformation is responsible for most of the degradation of penicillamine, and very little is excreted unchanged. Metabolites are found in both urine and feces. 

Penicillamine (CUPRIMINE, DEPEN) is available for oral administration. For chelation therapy, the usual adult dose is 11.5 g/day in 4 divided doses (see sections under individual metals). The drug should be given on an empty stomach to avoid interference by metals in food. 

B. Several drugs (eg, antacids and ferrous sulfate) and food can substantially reduce gastrointestinal absorption of penicillamine. 

Penicillamine Antacids (containing Ap and/or Mg ), iron compounds, food Formation of less soluble penicillamine chelates resulting in reduced absorption of penicillamine... 

Osman MA, Patel RB, Schuna A, Sundstrom WR, Welling PG Reduction in oral penicillamine absorpticm by food, antacid and ferrous sulii ate. Clin Pharmacol Ther( 9Z ) 33,465-70. 

Food can reduce the absorption of penicillamine by as much as a half. 

The presence of food reduced the plasma levels of penicillamine 500 mg by about 50% in healthy subjects. The total amount absorbed was similarly reduced. These figures are in good agreement with previous findings. ... 

Uncertain. One suggestion is that food delays gastric emptying so that the penicillamine is exposed to more prolonged degradation in the stomach. Another idea is that the protein in food reduces penicillamine absorption. 

An established interaction. If maximal effects are required the penicillamine should be taken at least 30 minutes before food. 

Schuna A, Osman MA, Patel RB, WelUng PG, Sundstrom WR. Influence of food on the bioavailability of penicillamine. JRheumatol 10, 95-7. 

Although the rarity of Wilson s disease made it commercially unprofitable, it proved possible to induce a pharmaceutical company to manufacture D-penicillamine. In 1963 the United States Food and Drug Administration approved penicillamine as safe and effective in the treatment of Wilson s disease. 

An active substance, although initially released from its dosage form (and dissolved), may become unavailable for absorption due to reactimis with other medicines or food components [4]. An example is the formation of insoluble complexes of tetracycline with calcium or aluminium ions from antacids or milk products. Interaction (chelation or binding) with iron ions leads to a reduced absorption for a variety of active substances such as doxycycline, penicillamine, methyldopa and ciprofloxacin. The absorption of active substances showing pH-dependent dissolution behaviour may be influenced by medicines that influence the gastric pH, such as H2-antagonists, proton pump inhibitors and antacids. Antimycotic active substances such as ketoconazole or itraconazole dissolve better in acidic fluids. Therefore their bioavailability may be increased by the concomitant use of an acidic drink like cola, whereas the concomitant use of antacids or proton pump inhibitors is likely to reduce the bioavailability. Concomitant use of milk may increase the dissolution of acidic active substances, whereas fats from food may increase the bioavailability of lipophilic active substances like albendazole and griseofulvin. 

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