The Experts below are selected from a list of 62319 Experts worldwide ranked by ideXlab platform
Brian G Lake - One of the best experts on this subject based on the ideXlab platform.
-
Effect of Pyrethrins on cytochrome P450 forms in cultured rat and human hepatocytes.
Toxicology, 2007Co-Authors: Roger J Price, Amanda M Giddings, Mary P Scott, David G Walters, Charles C Capen, Thomas G Osimitz, Brian G LakeAbstract:High doses of Pyrethrins produce liver and thyroid gland tumours in rats by modes of action involving the induction of hepatic xenobiotic metabolising enzymes. The aim of this study was to compare the effects of Pyrethrins with those of the rat liver and thyroid tumour promoter sodium Phenobarbital on some cytochrome P450 (CYP) forms in cultured rat and human hepatocytes. The treatment of female Sprague-Dawley rat and human (both male and female) hepatocytes for 72 h with 0-1000 microM Pyrethrins and 0-1000 microM Phenobarbital did not result in any marked cytotoxicity. In rat hepatocytes both Pyrethrins and Phenobarbital produced an induction of 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylase activity (a CYP1A/2B form marker) and CYP2B1 and CYP2B1/2 mRNA levels. Pyrethrins and Phenobarbital also induced CYP3A-dependent testosterone 6beta-hydroxylase activity in rat hepatocytes. In human hepatocytes Pyrethrins and Phenobarbital induced both testosterone 6beta-hydroxylase activity and CYP3A4 mRNA levels and also increased CYP2B6 mRNA levels. The effects of Pyrethrins and Phenobarbital were concentration-dependent and exhibited a threshold. These results demonstrate that the effects of Pyrethrins on CYP forms in cultured rat and human hepatocytes are qualitatively similar to those of Phenobarbital. Pyrethrins induce CYP2B and CYP3A forms in cultured rat hepatocytes and can induce CYP3A and CYP2B forms in human hepatocytes. While CYP form induction by Pyrethrins, Phenobarbital and related compounds can be associated with liver and thyroid gland tumour formation in rodents, epidemiological data for Phenobarbital suggests that such effects do not occur in humans.
-
Effect of Pyrethrins on cytochrome P450 forms in cultured rat and human hepatocytes.
Toxicology, 2007Co-Authors: Roger J Price, Amanda M Giddings, Mary P Scott, David G Walters, Charles C Capen, Thomas G Osimitz, Brian G LakeAbstract:Abstract High doses of Pyrethrins produce liver and thyroid gland tumours in rats by modes of action involving the induction of hepatic xenobiotic metabolising enzymes. The aim of this study was to compare the effects of Pyrethrins with those of the rat liver and thyroid tumour promoter sodium Phenobarbital on some cytochrome P450 (CYP) forms in cultured rat and human hepatocytes. The treatment of female Sprague–Dawley rat and human (both male and female) hepatocytes for 72 h with 0–1000 μM Pyrethrins and 0–1000 μM Phenobarbital did not result in any marked cytotoxicity. In rat hepatocytes both Pyrethrins and Phenobarbital produced an induction of 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylase activity (a CYP1A/2B form marker) and CYP2B1 and CYP2B1/2 mRNA levels. Pyrethrins and Phenobarbital also induced CYP3A-dependent testosterone 6β-hydroxylase activity in rat hepatocytes. In human hepatocytes Pyrethrins and Phenobarbital induced both testosterone 6β-hydroxylase activity and CYP3A4 mRNA levels and also increased CYP2B6 mRNA levels. The effects of Pyrethrins and Phenobarbital were concentration-dependent and exhibited a threshold. These results demonstrate that the effects of Pyrethrins on CYP forms in cultured rat and human hepatocytes are qualitatively similar to those of Phenobarbital. Pyrethrins induce CYP2B and CYP3A forms in cultured rat hepatocytes and can induce CYP3A and CYP2B forms in human hepatocytes. While CYP form induction by Pyrethrins, Phenobarbital and related compounds can be associated with liver and thyroid gland tumour formation in rodents, epidemiological data for Phenobarbital suggests that such effects do not occur in humans.
Varsha Bhattmehta - One of the best experts on this subject based on the ideXlab platform.
-
population pharmacokinetics of Phenobarbital in infants with neonatal encephalopathy treated with therapeutic hypothermia
Pediatric Critical Care Medicine, 2013Co-Authors: Renee A Shellhaas, Christina H Dillon, John D E Barks, Varsha BhattmehtaAbstract:OBJECTIVE Phenobarbital is the first-line treatment for neonatal seizures. Many neonates with hypoxic ischemic encephalopathy are treated with therapeutic hypothermia, and about 40% have clinical seizures. Little is known about the pharmacokinetics of Phenobarbital in infants with hypoxic ischemic encephalopathy who undergo therapeutic hypothermia. The objective of this study was to determine the effect of therapeutic hypothermia on Phenobarbital pharmacokinetics, taking into account maturational changes. SETTING Level 3 neonatal ICU. PATIENTS Infants with hypoxic ischemic encephalopathy and suspected seizures, all treated with Phenobarbital. Some of these infants also received treatment with therapeutic hypothermia. INTERVENTIONS None. DESIGN A retrospective cohort study of 39 infants with hypoxic ischemic encephalopathy treated with Phenobarbital (20 were treated with therapeutic hypothermia and 19 were not). MEASUREMENTS AND MAIN RESULTS Data on Phenobarbital plasma concentrations were collected in 39 subjects with hypoxic ischemic encephalopathy with or without therapeutic hypothermia. Using nonlinear mixed-effects modeling, population pharmacokinetics of Phenobarbital were developed with a total of 164 plasma concentrations. A one-compartment model best described the pharmacokinetics. The clearance of Phenobarbital was linearly related to body weight and matured with increasing age with a maturation half-life of 22.1 days. Therapeutic hypothermia did not influence the pharmacokinetic parameters of Phenobarbital. CONCLUSIONS Therapeutic hypothermia does not influence the clearance of Phenobarbital after accounting for weight and age. Standard Phenobarbital dosing is appropriate for the initial treatment of seizures in neonates with hypoxic ischemic encephalopathy treated with therapeutic hypothermia.
Biff F. Palmer - One of the best experts on this subject based on the ideXlab platform.
-
Effectiveness of hemodialysis in the extracorporeal therapy of Phenobarbital overdose
American Journal of Kidney Diseases, 2000Co-Authors: Biff F. PalmerAbstract:Abstract Most patients with Phenobarbital overdose can be adequately treated with general supportive care, cathartics, activated charcoal, and a forced alkaline diuresis. In severely compromised patients, both hemodialysis and hemoperfusion have been used to enhance elimination of the drug. Of these two therapies, hemoperfusion is generally considered to be more effective because Phenobarbital shows significant protein binding. Prior reports describing the use of hemodialysis in the treatment of Phenobarbital overdose used small low-efficiency dialyzers at much lower blood flow rates compared with what is available today. In this report, a patient with life-threatening Phenobarbital overdose is described who was treated with hemodialysis. This is the first reported case describing the effects of a high-efficiency dialyzer using high blood flow rates on Phenobarbital pharmakokinetics. Using this technique, the clearance of Phenobarbital was found to be greater than what has been previously reported with hemodialysis and greater than most reported cases describing the use of hemoperfusion. The procedure was associated with a rapid fall in Phenobarbital levels and a dramatic improvement in the patient's clinical condition. The findings in this case show that use of a high-efficiency dialyzer with high blood flow rates is an effective therapy for patients with life-threatening Phenobarbital poisoning. The excellent clearance of Phenobarbital shown in this case, combined with the lack of thrombocytopenia, more widespread availability, and greater familiarity by the staff who administer it, support the idea that hemodialysis should be considered the preferred mode of extracorporeal therapy for Phenobarbital intoxication.
Michel Guillaume - One of the best experts on this subject based on the ideXlab platform.
-
Effects of felbamate on the pharmacokinetics of Phenobarbital
Clinical pharmacology and therapeutics, 1995Co-Authors: Pascale Reidenberg, Paul Glue, Christopher Banfield, Robert D. Colucci, Jeffrey W. Meehan, Elaine Radwanski, Parviz Mojavarian, Chin-chung Lin, James Nezamis, Michel GuillaumeAbstract:The effects of felbamate on the pharmacokinetics of Phenobarbital and one of its main metabolites, parahydroxyPhenobarbital, were assessed in a parallel-group, placebo-controlled, double-blind study, in 24 healthy volunteers. Pharmacokinetic parameters of Phenobarbital and parahydroxyPhenobarbital were determined from plasma and urine samples obtained after 28 days of daily administration of 100 mg Phenobarbital and after a further 9 days of Phenobarbital plus 2400 mg/day felbamate or placebo. Felbamate increased Phenobarbital values for area under the plasma concentration-time curve from 0 to 24 hours and maximum concentration by 22% and 24%, respectively, whereas placebo had no effect. This increase was caused by a reduction in parahydroxylation of Phenobarbital and possibly through effects on other metabolic pathways. Because felbamate inhibits the S-mephenytoin hydroxylase (CYP2C19) isozyme in vitro, it appears that Phenobarbital hydroxylation is mediated in part by this isozyme. Clinical Pharmacology & Therapeutics (1995) 58, 279–287; doi:
Roger J Price - One of the best experts on this subject based on the ideXlab platform.
-
Effect of Pyrethrins on cytochrome P450 forms in cultured rat and human hepatocytes.
Toxicology, 2007Co-Authors: Roger J Price, Amanda M Giddings, Mary P Scott, David G Walters, Charles C Capen, Thomas G Osimitz, Brian G LakeAbstract:High doses of Pyrethrins produce liver and thyroid gland tumours in rats by modes of action involving the induction of hepatic xenobiotic metabolising enzymes. The aim of this study was to compare the effects of Pyrethrins with those of the rat liver and thyroid tumour promoter sodium Phenobarbital on some cytochrome P450 (CYP) forms in cultured rat and human hepatocytes. The treatment of female Sprague-Dawley rat and human (both male and female) hepatocytes for 72 h with 0-1000 microM Pyrethrins and 0-1000 microM Phenobarbital did not result in any marked cytotoxicity. In rat hepatocytes both Pyrethrins and Phenobarbital produced an induction of 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylase activity (a CYP1A/2B form marker) and CYP2B1 and CYP2B1/2 mRNA levels. Pyrethrins and Phenobarbital also induced CYP3A-dependent testosterone 6beta-hydroxylase activity in rat hepatocytes. In human hepatocytes Pyrethrins and Phenobarbital induced both testosterone 6beta-hydroxylase activity and CYP3A4 mRNA levels and also increased CYP2B6 mRNA levels. The effects of Pyrethrins and Phenobarbital were concentration-dependent and exhibited a threshold. These results demonstrate that the effects of Pyrethrins on CYP forms in cultured rat and human hepatocytes are qualitatively similar to those of Phenobarbital. Pyrethrins induce CYP2B and CYP3A forms in cultured rat hepatocytes and can induce CYP3A and CYP2B forms in human hepatocytes. While CYP form induction by Pyrethrins, Phenobarbital and related compounds can be associated with liver and thyroid gland tumour formation in rodents, epidemiological data for Phenobarbital suggests that such effects do not occur in humans.
-
Effect of Pyrethrins on cytochrome P450 forms in cultured rat and human hepatocytes.
Toxicology, 2007Co-Authors: Roger J Price, Amanda M Giddings, Mary P Scott, David G Walters, Charles C Capen, Thomas G Osimitz, Brian G LakeAbstract:Abstract High doses of Pyrethrins produce liver and thyroid gland tumours in rats by modes of action involving the induction of hepatic xenobiotic metabolising enzymes. The aim of this study was to compare the effects of Pyrethrins with those of the rat liver and thyroid tumour promoter sodium Phenobarbital on some cytochrome P450 (CYP) forms in cultured rat and human hepatocytes. The treatment of female Sprague–Dawley rat and human (both male and female) hepatocytes for 72 h with 0–1000 μM Pyrethrins and 0–1000 μM Phenobarbital did not result in any marked cytotoxicity. In rat hepatocytes both Pyrethrins and Phenobarbital produced an induction of 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylase activity (a CYP1A/2B form marker) and CYP2B1 and CYP2B1/2 mRNA levels. Pyrethrins and Phenobarbital also induced CYP3A-dependent testosterone 6β-hydroxylase activity in rat hepatocytes. In human hepatocytes Pyrethrins and Phenobarbital induced both testosterone 6β-hydroxylase activity and CYP3A4 mRNA levels and also increased CYP2B6 mRNA levels. The effects of Pyrethrins and Phenobarbital were concentration-dependent and exhibited a threshold. These results demonstrate that the effects of Pyrethrins on CYP forms in cultured rat and human hepatocytes are qualitatively similar to those of Phenobarbital. Pyrethrins induce CYP2B and CYP3A forms in cultured rat hepatocytes and can induce CYP3A and CYP2B forms in human hepatocytes. While CYP form induction by Pyrethrins, Phenobarbital and related compounds can be associated with liver and thyroid gland tumour formation in rodents, epidemiological data for Phenobarbital suggests that such effects do not occur in humans.
