Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 27-year-old woman who acquired cutaneous leishmaniasis in Central America was inadvertently treated with 10 times the intended daily dose of the pentavalent antimonial compound sodium stibogluconate (Pentostam): 8500 mg (143 mg/kg) instead of 850 mg. The patient felt "wiped out" during the 4-h infusion of the drug. After the mistake in dosing was discovered, she was vigorously hydrated and carefully monitored in an intensive care unit for greater than 48 h. Her vital signs were stable, and no arrhythmias were noted. Her alanine aminotransferase level rose briefly to 2.4 times the upper limit of normal, and her white blood cell count briefly fell 43% to a low of 3700/microliter. Her skin lesions subsequently healed without further therapy. Although sodium stibogluconate has been associated with a variety of side effects, in this case, a single high dose of the drug was tolerated without serious toxicity.
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PMID:Sodium stibogluconate (Pentostam) overdose during treatment of American cutaneous leishmaniasis. 131 73

Sodium stibogluconate is the mainstay of treatment for all forms of leishmaniasis. Therapy is associated with an increase in serum aminotransferases. In this study liver damage was assessed during treatment of American cutaneous leishmaniasis with sodium stibogluconate and also in a control group given aminosidine. In addition to standard liver function tests, acute hepatocellular damage was assessed by measuring plasma glutathione S-transferase B1 (GST), and hepatic metabolic capacity was assessed by a caffeine clearance (CCL) test, before, during and after treatment. Thirteen patients were treated; 5 received sodium stibogluconate, 6 received aminosidine and a further 2 patients received aminosidine followed by sodium stibogluconate. Treatment with sodium stibogluconate was associated with an increase in both alanine aminotransferase (ALT) and GST and a fall in the CCL, indicating both hepatocellular damage and functional impairment. Six weeks after treatment had stopped ALT and GST had returned to pre-treatment levels and the CCL remained depressed in only one patient. Patients given aminosidine did not show any evidence of liver damage. Sodium stibogluconate is associated with significant hepatocellular damage and hepatic functional impairment. However, this is rapidly reversible on drug withdrawal. We suggest that liver function is monitored throughout treatment and that patients with pre-existing liver disease receive alternative treatment.
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PMID:Hepatotoxicity of sodium stibogluconate therapy for American cutaneous leishmaniasis. 757 Aug 43

The pentavalent antimonial compounds Glucantime and Pentostam are the first line drugs used in anti-Leishmania treatment. However, no in vivo studies have compared the efficacy and toxicity of these drugs where host variability has been controlled. Biochemical studies of Leishmania have detected differences between the two drugs with regard to DNA topoisomerase I inhibition, a phenomenon that possibly impacts treatment efficacy. To evaluate the clinical efficacy, hamsters were infected intradermally in the right hind foot with 10(6) promastigotes of a wild type or luciferase-transfected Leishmania panamensis. At three weeks post-inoculation, the animals were treated intramuscularly with either Glucantime or Pentostam (30, 60 or 120 mg SbV/kg per day for 20 days). To evaluate parasitological efficacy a luminometry assay was standardized for quantitation of amastigotes in hamster tissues. To evaluate toxicity, hamsters were treated intramuscularly with Glucantime or Pentostam (120, 160 or 240 mg SbV/kg per day for 20 days). Animals inoculated with either of the parasite strains and treated with either drug, showed a similar rate of lesion reduction, as compared to untreated controls (p<0.01). Parasite burden was also comparable, and no significant differences were found in the cure rate. No renal or hepatic alterations occurred as evidenced by normal serum levels of creatinine, aspartate aminotransferase, alanine aminotransferase and amylase. Hamsters treated with 120 mg SbV/kg per day for 20 days or higher doses of Pentostam showed macro- and microscopic signs of inflammation at the site of injection. These effects were absent in the animals treated with Glucantime. The results confirmed clinical observations regarding the similar efficacy of the two drugs, as well as the higher local toxicity of Pentostam.
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PMID:[Efficacy and toxicity of pentavalent antimonials (Glucantime and Pentostam) in an American cutaneous leishmaniasis animal model: luminometry application]. 1567 3