Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

OBJECTIVE: To evaluate the pharmacokinetics of cefetamet pivoxil and possible interaction with N-acetylcysteine and cisapride in healthy volunteers. METHODS: In a double-blind, randomized three-way crossover study with 12 healthy male volunteers, serum and urine concentrations of cefetamet were determined over 12 h by a validated bioassay method after oral administration of 0.5 g cefetamet pivoxil and, randomly, placebo, 5x20 mg cisapride, or 0.6 g N-acetylcysteine. RESULTS: The study medications were well tolerated, although there were 10 cases of altered bowel movements, two cases of mild, transient headache and one case of increased serum transferase levels (AST and ALT). The mean peak serum level of cefetamet pivoxil in the placebo group was 4.86plus minus1.35 mg/L. The urine recovery/24 h in the placebo group was 41.9plus minus3.8% of the oral dose. The elimination half-life was 3.56plus minus0.92 h. N-Acetylcysteine had no effect on the pharmacokinetics of cefetamet pivoxil. With concomitant administration of cisapride there was an accelerated absorption of cefetamet pivoxil and a slightly increased Cmax of cefetamet. The Cmax values differed significantly (p<0.05) only between the cisapride group (5.76plus minus1.50 mg/L) and the N-acetylcysteine group (4.53plus minus1.18 mg/L). CONCLUSION: None of the small pharmacokinetic differences between the three groups is expected to have any relevance in the treatment of infectious diseases with cefetamet pivoxil.
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PMID:Pharmacokinetics of cefetamet pivoxil and interaction with cisapride and N-acetylcysteine. 1186

A multicenter, open labeled, randomized early Phase II study for CGS 20267 was conducted at the doses 0.5 mg once daily and 1.0 mg once daily in postmenopausal women with advanced breast cancer. Sixty-four patients were randomly assigned to the doses of either 0.5 mg once daily (n = 33) or 1.0 mg once daily (n = 31). Thirty-one patients were eligible for 0.5 mg group, and 29 for 1.0 mg group. A total of 57 patients (30 in the 0.5 mg group and 27 in the 1.0 mg group) were eligible for the evaluation of efficacy. There were 3 CR, 5 PR, 5 stable disease (SD: NC lasting over 24 weeks), 7 NC and 10 PD in the 0.5 mg group. The objective response rate (ORR) was 26.7%. There were 4 CR, 7 PR, 8 SD, 3 NC and 5 PD in the 1.0 mg group. The ORR was 40.7%. A total of 57 patients (29 in the 0.5 mg group and 28 in the 1.0 mg group) were eligible for safety evaluation. Adverse clinical events related to CGS 20267 in the 0.5 mg group were headache, nausea, cold sweat, sleepiness and muscle ache in the lower extremities (2 patients, incidence rate 6.9%) whereas those in the 1.0 mg group were generalized itching and generalized hot feeling (2 patients, incidence rate 7.1%). All of the adverse events were grade 1 except the generalized itching which was grade 2. CGS 20267-related abnormalities in the laboratory tests for the 0.5 mg group were a decrease in WBC, and increases in GOT, GPT, LDH and gamma-GTP (5 patients, 14.3%) whereas those in the 1.0 mg group were increases in GPT, gamma-GTP, alkaline phosphatase, and total bilirubin (1 patient, 3.6%). The increases in GOT and GPT were grade 2, but others were grade 1. The data show both CGS 20267 0.5 mg once daily and 1.0 mg once daily to be effective and tolerable in the treatment of postmenopausal women with advanced breast cancer.
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PMID:[CGS 20267 (Letrozole), a new aromatase inhibitor: early phase II study for postmenopausal women with advanced breast cancer]. 1197 39

A multiple-dose administration study of exemestane (0.5-50 mg/day after breakfast for 7 days) was conducted in 32 normal healthy postmenopausal Japanese women using a single-blind, 3-step dose-titration method in order to investigate the safety, effect on serum concentration, amount of urinary estrogen excretion, and pharmacokinetics of the drug. Subjective/objective symptoms, in which a causal relationship with exemestane administration could not be excluded, were as follows: headache (8 cases: 1 each in the 0.5 and 25 mg groups, 2 in the 10 mg group and 4 in the 50 mg group), dizziness (2 cases: 1 each in the 0.5 and 25 mg groups), and fever (1 in the 25 mg group), all of which were mild and disappeared without treatment. The only abnormal laboratory findings were a mild increase in levels of GOT and GPT in 1 case and in the number of basophils in another case. There were no notable abnormal findings in vital signs, body weight or EKG. A dose-dependent decrease in serum estrogen level was observed between doses of 0.5 mg and 25 mg. The decrease was maximal at 25 mg, at which serum estrogen concentrations decreased to 14-27% of those observed at day 0. This decrease was maintained for one week, returning to baseline levels 2 weeks after the completion of drug administration. A similar result was also observed in the suppression of 24-hour urinary estrogen excretion. Exemestane was absorbed immediately after initial administration, reaching Cmax 0.9-2.6 hours post-administration. This was followed by a rapid decrease over the next 4-8 hours followed by a gradual decrease Cmax reached normal steady state values on day 5. Cmax and AUC0-24 values taken between administration of the first and final doses increased proportionally in a dose-dependent manner, suggesting that exemestane has a linear pharmacokinetic profile. Furthermore, results of the comparison of the trough concentrations of the initial dose with those of the final dose suggested no accumulative effects of the study drug.
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PMID:[Phase I multiple-dose administration study of exemestane in postmenopausal women]. 1214

Exemestane was administered orally to postmenopausal women with advanced/recurrent breast cancer at a dose of 10 mg/day or 25 mg/day once daily for more than 8 weeks in order to evaluate the drug's anti-tumor effects and safety in a dose-finding study. The response rate (CR + PR) in the 10 mg and 25 mg group was 25.0% (8/32) and 31.4% (11/35), respectively, demonstrating no significant differences between the two groups, yet a higher efficacy rate was observed in 25 mg group. The efficacy rate in hormone-treatment-resistant patients within the 10 mg and 25 mg groups was 14.3% (3/21) and 26.1% (6/23), respectively, demonstrating more than a 20% response rate in 25 mg group. Incidences of the adverse events of which relevance to the drug could not be excluded were 30.6% (11/36) in the 10 mg group. 13.9% (5/36) in the 25 mg group and 22.2% (16/72) in the total group. The major adverse events were, hot flashes, numbness of the limbs, nausea, headache etc. Abnormal findings in clinical laboratory tests were as follows: ALP increase; GOT increase; GPT increase; gamma-GTP increase; total cholesterol increase; urinary sediment present. Abnormal findings in endocrine function were as follows: aldosterone decrease; testosterone.cortisol.DHEA-S decrease. But discontinuation due to abnormal laboratory findings was not found. No abnormal findings in physical tests were observed. A significant decrease in plasma estrogen concentration at week 4 was observed in both the 10 mg and 25 mg groups compared with baseline. These low levels were maintained throughout the study period. On the basis of these results, the efficacy of exemestane 25 mg/day was verified to be slightly higher than 10 mg/day. In addition the safety profile had no major adverse events to notice. In these patients with advanced/recurrent breast cancer, 25 mg/day was recommended as the most appropriate dose to be used clinically.
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PMID:[Early phase II dose-finding study of exemestane in postmenopausal patients with advanced/recurrent breast cancer]. 1214 1

Mycophenolate mofetil (MMF) is an immunosuppressive agent that is widely used in the management of liver transplant recipients. MMF inhibits the inosine monophosphate dehydrogenase that has been shown to have in vitro antiviral properties against flaviviruses, suggesting the possibility that it might also inhibit the hepatitis C virus (HCV). The goal of this short-term dose escalation study was to assess the antiviral effects of MMF on HCV replication. Patients with chronic hepatitis C who had not undergone liver transplantation were randomized to 8 weeks of treatment with one of four mycophenolate dose regimens (1000 mg orally twice daily, 500 mg orally twice daily, 250 mg orally twice daily, or a matched oral placebo twice daily). All groups were double-blinded. Quantitative HCV RNA levels and serum alanine aminotransferase were assessed at baseline, at weeks 2, 4, and 8 of dosing, and at weeks 4 and 8 of follow-up. Thirty patients met inclusion criteria, enrolled, and were randomized. HCV RNA levels did not change significantly during treatment. Specifically, no subject became virus negative or had a one-log decrease in virus level. Serum aminotransferase level did not normalize in any subject. The most common side effects were headache, nausea, and diarrhea. Mycophenolate alone does not appear to have a significant antiviral or biochemical effect in patients with chronic hepatitis C.
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PMID:Lack of antiviral effect of a short course of mycophenolate mofetil in patients with chronic hepatitis C virus infection. 1251 74

We report a 52 years old male admitted for fever lasting one month, dry cough, headache and malaise. Initial laboratory work up showed an AST of 172 U/l, and ALT of 252 U/l, a GGT of 353 U/l and alkaline phosphatases of 952 U/l. An abdominal CAT scan disclosed a mild hepatosplenomegaly. A liver biopsy showed a granulomatous hepatitis. During the evolution, the patient had a left testicle swelling with darkening of the surrounding skin. A testicular ultrasound showed a bilateral orchiepidydimitis. The patient was treated with non steroidal anti-inflammatory drugs and fever subsided. Three months later, these drugs were discontinued and the patient remained asymptomatic and with normal laboratory values until 36 months of follow up.
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PMID:[Idiopathic granulomatous hepatitis with bilateral orchiepididymitis and skin eruption]. 1258 10

Recombinant human interleukin 12 (IL-12) is an immunomodulatory cytokine that is active against several viruses. Treatment options in patients with chronic hepatitis C with nonresponse to interferon (IFN)-based therapy are limited. Prior dose-ranging studies have indicated drug tolerability and transient suppression of hepatitis C virus (HCV) RNA by IL-12. The aim of this study was to determine the safety and efficacy of prolonged IL-12 therapy in patients who have failed treatment with IFN-alpha +/- ribavirin. A total of 225 patients at 21 U.S. sites who had a history of nonresponse to IFN-alpha or combination IFN-alpha plus ribavirin for treatment of HCV were randomized to 500 ng/kg IL-12 or placebo subcutaneously twice weekly for 12 weeks. The groups were then unblinded; patients receiving IL-12 continued for another 36 weeks, and the placebo group received 48 weeks of treatment with IL-12 in an open-label fashion. HCV RNA, serum alanine aminotransferase (ALT) level, and a repeat liver biopsy were assessed at 24 weeks following therapy. Approximately 1% (2 of 160) of nonresponsive patients enrolled for treatment had a sustained virologic response to IL-12 therapy, but 3% (7 of 225) developed severe adverse events probably related to treatment, resulting in early termination of the trial. Common adverse effects reported by most patients included chills, fever, fatigue, headache, and arthralgia. At termination of the study, 160 patients had received at least 8 weeks of treatment with IL-12. Paired liver biopsy specimens were available for evaluation in 54 patients, but there were no significant changes in Knodell fibrosis or histologic activity index (HAI) scores. In conclusion, IL-12 as monotherapy at the doses used in this trial for chronic hepatitis C has low efficacy, was poorly tolerated, and is unlikely to provide an alternative to conventional IFN-based therapy.
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PMID:A multicenter study of recombinant human interleukin 12 for the treatment of chronic hepatitis C virus infection in patients nonresponsive to previous therapy. 1277 16

We examined the clinical symptoms and laboratory findings of 21 children with aseptic meningitis caused by echovirus 13 during the summer of 2002. All patients (mean age: 8.3 years) complained of fever and headache. Some had mild vomiting and some had severe vomiting of 4 times or more. In the early stage of the disease, the mean count of WBC was 8,283/microliter, mean level of CRP was 0.8 mg/dl, and there were no abnormalities in levels of GOT, GPT, or LDH. The levels of protein and sugar, in cerebrospinal fluid showed no abnormalities, and mean total cell count was 560/microliter. The mean number of polynuclear cells was 357/microliter, and of mononuclear cells was 203/microliter, showing polynuclear cell predominance. In the recovery period, the tendency to polynuclear cell predominance in the early stage of the disease shifted to mononuclear predominance. One of the 21 patients exhibited multinucleated cell predominance in the cerebrospinal fluid, a high CRP value of 6.2 mg/dl, as well as symptoms of restlessness including numbness of the limbs, hyperpnea, and excitation, needed careful diagnosis as aseptic meningitis. Almost all of the patients were mild cases, and no large differences were seen with the clinical and laboratory findings in previous reports of echovirus aseptic meningitis.
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PMID:[Clinical analysis of aseptic meningitis caused by echovirus 13]. 1457 43

Between the dates of May 4th-August 6th 2002, 46 cases were detected with abdominal pain nausea, vomiting, arthralgia/myalgia, headache, fever, diarrhea and rash, in the middle Blacksea and north inner Anatolia regions. Their laboratory findings yielded elevated levels of liver enzymes (AST, ALT, LDH), leucopenia and thrombocytopenia. As the infection was treated easily with tetracyclines, clinical diagnosis was considered to be rickettsiosis or ehrlichiosis. Serum and blood samples obtained from some of the patients were tested against Rickettsia, Ehrlichia, Leptospira and Coxiella, in the national and international laboratories. Samples from 19 patients were sent to National Reference Centre and WHO Collaborating Centre for Rickettsial Reference and Research Laboratory, France, and 7 of them were reported as acute Q fever while 8 of them were reported as passed Q fever (QF) cases. In May 2003, new cases with similar symptoms have been reported from the same regions, with different epidemiologic and serologic findings (tick exposure history was higher, response to tetracycline was lower, C. burnetii antibodies were negative), indicating a viral etiology. The samples of these patients have been sent to National Reference Centre and WHO Collaborating Centre for Arboviruses and Viral Heamorrhagic Fevers, France, and the initial reports were marked as Crimean Congo hemorrhagic fever virus (CCHFV). Then the serum samples of previous 26 patients which were stored in National Serum Bank have been retrospectively investigated for viral aetiology in the same center, and 17 of them have been found positive for CCHFV IgM antibodies. Four of these patients were diagnosed as acute QF in 2002, one was passed QF, 2 were negative for QF and 10 were patients not investigated for QF. As a result, the detection of the both infections together in the same area shows the essential need for further epidemiological investigations.
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PMID:[Epidemiological evaluation of a possible outbreak in and nearby Tokat province]. 1529

A study in healthy men and women was performed to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of orally administered recombinant human interleukin-11 (oprelvekin) (OAO). Four cohorts of 10 subjects each received 3, 5, 10 or 30 mg (8:2/OAO:placebo ratio), first as a single dose with a 7-day washout period, then 7 consecutive daily doses. Safety was assessed by ongoing evaluation of adverse events (AEs) and laboratory values. PK samples were collected on the first and last day of dose administration. The established effects of subcutaneous oprelvekin on C-reactive protein (CRP, upward arrow), platelet count (upward arrow), fibrinogen (upward arrow) and hemoglobin (downward arrow), were evaluated. PK analysis showed that most subjects (27/34, 79%) had undetectable serum levels of IL-11. PD measures showed no changes from baseline between any OAO group and the placebo group. Orally administered oprelvekin was safe and well tolerated at all doses. A total of five AEs (abdominal pain, diarrhea, headache, rhinitis, grade 3 alanine aminotransferase elevation) were reported across all groups. Evaluations of serum IL-11 levels indicate that OAO is not systemically absorbed at levels above the lower limit of the bioanalytic assay. These data in addition to the lack of effect on PD measures suggest that there is a decreased potential of systemic adverse events with OAO.
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PMID:A multiple-dose, safety, tolerability, pharmacokinetics and pharmacodynamic study of oral recombinant human interleukin-11 (oprelvekin). 1538 78


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