Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

9-(beta-D-1,3-Dioxolan-4-yl)guanine (DXG) exhibits potent antiviral activity against human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV) in vitro. However, since DXG possesses limited aqueous solubility, a more water soluble prodrug of DXG, 9-(beta-D-1,3-dioxolan-4-yl)-2-aminopurine (APD), was synthesized. The purpose of this study was to characterize the pharmacokinetics of APD and its antiviral metabolite DXG in mice. Female NIH-Swiss mice were administered 100 mg/kg APD intravenously or orally. Serum, brain and liver were collected at selected times following prodrug administration and concentrations of APD and DXG were determined by HPLC. APD was efficiently converted to parent nucleoside DXG following both intravenous and oral administration. Biotransformation of APD to DXG likely occurs in the liver and is mediated by xanthine oxidase. Similar pharmacokinetic profiles for DXG were observed following either route of administration in serum, liver and brain. These results demonstrate that APD appears to be a promising prodrug for the delivery of DXG.
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PMID:Biotransformation and pharmacokinetics of prodrug 9-(beta-D-1,3-dioxolan-4-yl)-2-aminopurine and its antiviral metabolite 9-(beta-D-1,3-dioxolan-4-yl)guanine in mice. 929 58

Nocardiosis is an opportunistic infection especially in patients with underlying chronic debilitating disease or immunodeficiency. Nocardia peritonitis is an uncommon infection in peritoneal dialysis patients. Here, we report a case of peritonitis by Nocardia asteroides during automated peritoneal dialysis in a 35-year-old male patient who had prolonged immunosuppressive therapy to treat acute rejection of a nonfunctioning kidney allograft. The patient presented at our outpatient clinic with typical symptoms of acute peritonitis. The peritoneal fluid leukocyte count was 20,500 cells/microL, with 90% neutrophils. Gram staining showed gram-positive filamentous bacilli later identified as N. asteroides. After bacterial identification, the patient received trimethoprim 320 mg and sulfamethoxazole 3200 mg intravenously every 48 hours (TMP-SMX), plus amikacin 100 mg intraperitoneally daily. The immunosuppressive therapy was reduced. Peritoneal fluid cultures became negative after 1 week of treatment, concomitant with clinical improvement. Unfortunately, after 5 weeks of therapy, the patient developed hematologic side effects attributable to the TMP-SMX treatment. The TMP-SMX was suspended at that time, and the patient then received cefuroxime 500 mg by mouth and amikacin 100 mg intraperitoneally daily for a total of 12 weeks. The patient recovered completely and was discharged 3 months after onset of the peritonitis. Prolonged antibiotic therapy without catheter removal has not been previously described in immunosuppressed patients with APD peritonitis. The combination of amikacin and TMP-SMX may be safe and effective in APD patients who develop N. asteroides peritonitis.
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PMID:Successful treatment of Nocardia asteroides peritonitis in a patient undergoing automated peritoneal dialysis and receiving immunosuppressive therapy. 1668 87