DL-Penicillamine (25 mg/kg; ip; twice daily, for 5 days) has antidotal benefits when combined with Prussian blue in rats with thallotoxicosis[2].

Animal/Disease Models: Male Wistar rats, NIH strain (intoxicated by ip injection of 32 mg/kg thallium (I) acetate)[2]
Doses: 25 mg/kg
Route of Administration: ip; twice (two times) daily, for 5 days
Experimental Results: diminished slightly the thallium content in blood, organs and brain. Increased the probability survival when co- treated with Prussian blue (50 mg/kg; po).

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Limited information indicates that penicillamine is not detectable in breastmilk and no adverse effects have been reported among breastfed infants whose mothers were taking the drug. Copper and zinc levels in breastmilk are reduced in some mothers receiving penicillamine. Penicillamine has been used with apparent safety during nursing of several infants. Based on available data, it appears that penicillamine is acceptable to use during breastfeeding.
◉ Effects in Breastfed Infants
One woman taking penicillamine 1500 mg daily for cystinuria breastfed her infant for 3 months with no apparent adverse effects in her infant.
A woman taking penicillamine in an unspecified dosage for Wilson’s disease breastfed her infant. The infant’s serum copper and zinc levels were normal. The infant fed well and developed normally.
Another woman breastfed 2 infants after 2 pregnancies while being treated for Wilson's disease with penicillamine 750 mg daily. One infant had prolonged icterus that was unlikely to have been related to the penicillamine.
A center in Türkiye reported 23 infants born to mothers with Wilson's disease over a 20-year period. Twenty-one were treated with penicillamine 600 mg and zinc 100 mg daily. All infants were breastfed (extent and duration not specified). One premature infant died at 3 weeks of age (maternal drug not specified), but the other infant had no apparent complications over a median of 51 months (range 13 to 105 months) of follow-up.
A center in Germany reports 32 patients with Wilson's disease who became pregnant. Thirteen of the patients were taking penicillamine in dosages of 600 to 1200 mg daily. Of the 31 women who delivered a live infant, 27 of them breastfed their infants (extent not stated). Four of the infants had neonatal jaundice, but its relationship to penicillamine cannot be determined. The exact number of women who breastfed while taking penicillamine is unclear in the report.
Seven patients with Wilson’s disease were taking penicillamine in dosages of 300 to 800 mg daily. Maternal reports indicate that all infants exhibited normal development.
◉ Effects on Lactation and Breastmilk
In some case reports and studies, milk concentrations of copper and zinc were reduced during therapy of Wilson's disease with penicillamine.
A more recent study compared copper concentration in the milk of 7 mothers taking penicillamine compared to 25 control mothers without Wilson’s disease. The copper concentration in the colostrum (0-4 days postpartum) of women treated with penicillamine was slightly higher than normal. Copper and zinc concentrations were normal in mature breastmilk (>14 days postpartum) from all mothers treated with penicillamine, despite lower copper concentrations in maternal serum.

[1]. TU J, BLACKWELL RQ, LEE PF. DL-penicillamine as a cause of optic axial neuritis. JAMA. 1963 Jul 13;185:83-6.

[2]. Additive effect of DL-penicillamine plus Prussian blue for the antidotal treatment of thallotoxicosis in rats. Environ Toxicol Pharmacol. 2011 Nov;32(3):349-55.

[3]. Huebner Kf, Gengozian N. Depression Of The Primary Immune Response By Dl-Penicillamine. Proc Soc Exp Biol Med. 1965 Feb;118:561-5.

Penicillamine is an alpha-amino acid having the structure of valine substituted at the beta position with a sulfanyl group. It is a non-proteinogenic alpha-amino acid and a thiol.
3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease.
See also: Penicillamine (annotation moved to); L-Penicillamine (annotation moved to).

C5H11NO2S

149.21

149.051

52-66-4

Penicillamine;52-67-5;Penicillamine-d3

4727

Solid powder

1.2±0.1 g/cm3

251.8±35.0 °C at 760 mmHg

208-212ºC

106.1±25.9 °C

0.0±1.1 mmHg at 25°C

1.528

0.93

3

4

2

9

124

0

VVNCNSJFMMFHPL-UHFFFAOYSA-N

InChI=1S/C5H11NO2S/c1-5(2,9)3(6)4(7)8/h3,9H,6H2,1-2H3,(H,7,8)

2-amino-3-methyl-3-sulfanylbutanoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O: 33.33 mg/mL (223.38 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

---

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

 (Please use freshly prepared in vivo formulations for optimal results.)