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Torben Hansen - One of the best experts on this subject based on the ideXlab platform.
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high heritability and genetic correlation of intravenous glucose and Tolbutamide induced insulin secretion among non diabetic family members of type 2 diabetic patients
Diabetologia, 2014Co-Authors: Anette P Gjesing, Malene Hornbak, Kristine H Allin, Claus Thorn Ekstrom, Soren A Urhammer, Hans Eiberg, Oluf Pedersen, Torben HansenAbstract:Aims/hypothesis The aim of this study was to estimate the heritability of quantitative measures of glucose regulation obtained from a Tolbutamide-modified frequently sampled IVGTT (t-FSIGT) and to correlate the heritability of the glucose-stimulated beta cell response to the Tolbutamide-induced beta cell response. In addition, single nucleotide polymorphisms (SNPs) having an exclusive effect on either glucose- or Tolbutamide-stimulated insulin release were identified.
Yuji Kurosaki - One of the best experts on this subject based on the ideXlab platform.
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efficacy of peritoneal dialysis of Tolbutamide in rats under conditions of the plasma unbound fraction being increased
Biopharmaceutics & Drug Disposition, 2009Co-Authors: Takashi Makita, Yuki Izuwa, Tetsuya Aiba, Yukiko Komori, Hiromu Kawasaki, Yuji KurosakiAbstract:Peritoneal dialysis of a highly protein-bound compound, Tolbutamide, was examined in rats to clarify whether the efficacy of the peritoneal dialysis of such compounds increases proportionally as their unbound fractions increase. As expected, it was shown that the Tolbutamide concentration of the peritoneal dialysate rose as the unbound fraction of Tolbutamide increased. However, the efficacy of peritoneal dialysis of Tolbutamide was proportionally elevated only when the unbound fraction was slightly increased by sulfamethoxazole treatment. When the unbound fraction of Tolbutamide was increased 7.8 times by sulfadimethoxine treatment, the dialysis efficacy was increased to only 58% of that expected. This discrepancy between the observed and expected values regarding dialysis efficacy was more marked when experiments were performed in rats with experimentally induced acute renal failure. Pharmacokinetic analysis indicated that the intrinsic dialysis clearance of Tolbutamide decreased when its unbound fraction was greatly increased. These findings suggest that peritoneal dialysis may be mediated not only by passive diffusion, but also by concentration-dependent processes. The efficacy of the peritoneal dialysis of therapeutic compounds may be overestimated if the estimation is based only on their unbound fraction measured under control conditions. Copyright © 2009 John Wiley & Sons, Ltd.
John O Miners - One of the best experts on this subject based on the ideXlab platform.
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Co-regulation of phenytoin and Tolbutamide metabolism in humans.
British journal of clinical pharmacology, 1992Co-Authors: Wongwiwat Tassaneeyakul, Maurice E Veronese, C J Doecke, Michael E Mcmanus, Donald J. Birkett, Lloyd Sansom, John O MinersAbstract:1. The disposition of phenytoin and Tolbutamide was compared in eighteen healthy young adults separately administered single therapeutic doses (sodium phenytoin 300 mg, Tolbutamide 500 mg) of the two drugs. 2. Within the group, ratios of ranges of total and unbound areas under the plasma concentration-time curves were similar for both drugs. 3. There were significant (P < 0.001) correlations between total (r = 0.88) and unbound (r = 0.86) areas under the plasma phenytoin and Tolbutamide concentration-time curves. 4. The results are consistent with the involvement of the same cytochrome P-450 isoenzyme(s) in the metabolism of Tolbutamide and phenytoin.
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relationship between phenytoin and Tolbutamide hydroxylations in human liver microsomes
British Journal of Clinical Pharmacology, 1991Co-Authors: C J Doecke, Maurice E Veronese, John O Miners, D J Birkett, S M Pond, L N Sansom, Michael E McmanusAbstract:1. The metabolic interaction of phenytoin and Tolbutamide in human liver microsomes was investigated. 2. Phenytoin 4-hydroxylation (mean Km 29.6 microM, n = 3) was competitively inhibited by Tolbutamide (mean Ki 106.2 microM, n = 3) and Tolbutamide methylhydroxylation (mean Km 85.6 microM, n = 3) was competitively inhibited by phenytoin (mean Ki 22.6 microM, n = 3). 3. A significant correlation was obtained between phenytoin and Tolbutamide hydroxylations in microsomes from 18 human livers (rs = 0.82, P less than 0.001). 4. Sulphaphenazole was a potent inhibitor of both phenytoin and Tolbutamide hydroxylations with IC50 values of 0.4 microM and 0.6 microM, respectively. 5. Mephenytoin was a poor inhibitor of both phenytoin and Tolbutamide hydroxylations with IC50 values greater than 400 microM for both reactions. 6. Anti-rabbit P450IIC3 IgG inhibited both phenytoin and Tolbutamide hydroxylations in human liver microsomes by 62 and 68%, respectively. 7. These in vitro studies are consistent with phenytoin 4-hydroxylation and Tolbutamide methylhydroxylation being catalysed by the same cytochrome P450 isozyme(s) in human liver microsomes.
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validation of the Tolbutamide metabolic ratio for population screening with use of sulfaphenazole to produce model phenotypic poor metabolizers
Clinical Pharmacology & Therapeutics, 1990Co-Authors: Maurice E Veronese, John O Miners, David Randles, Debbie Gregov, D J BirkettAbstract:The present study has validated kinetically a convenient method to measure Tolbutamide hydroxylation capacity in human beings by use of urinary metabolic ratios. The known in vivo and in vitro inhibitory properties of sulfaphenazole were used to convert control phase subjects to phenotypically “poor” metabolizers of Tolbutamide. Six healthy subjects were given a single 500 mg oral dose of Tolbutamide with and without sulfaphenazole, 500 mg every 12 hours. Tolbutamide, hydroxyTolbutamide, and carboxyTolbutamide in urine were determined by newly developed HPLC procedures. Plasma Tolbutamide clearance and half-life were measured, as were the metabolic ratio (hydroxyTolbutamide + carboxyTolbutamide/Tolbutamide) in successive 6-hour urine collections. The mean Tolbutamide plasma clearance decreased from 0.196 ± 0.026 ml/min/kg without sulfaphenazole to 0.039 ± 0.009 ml/min kg with sulfaphenazole, and the mean half-life of Tolbutamide increased from 7.28 ± 0.89 hours to 38.76 ± 13.30 hours. The metabolic ratio determined in the 6 to 12 hour urine collection period decreased from 794.0 ± 86.6 to 126.0 ± 79.3, and this collection period also gave the best separation of subjects between phases. There was a good correlation between Tolbutamide plasma clearance and metabolic ratio (rs = 0.853, p < 0.01, n = 12) and between the percentage decrease in plasma Tolbutamide clearance and the percentage decrease in metabolic ratio (r = 0.932, p < 0.01, n = 6). The Tolbutamide urinary metabolic ratio therefore effectively distinguishes Tolbutamide hydroxylase activity in “normal” subjects and in those converted to model phenotypically “poor” metabolizers by sulfaphenazole. Clinical Pharmacology and Therapeutics (1990) 47, 403–411; doi:10.1038/clpt.1990.46
Maurice E Veronese - One of the best experts on this subject based on the ideXlab platform.
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Co-regulation of phenytoin and Tolbutamide metabolism in humans.
British journal of clinical pharmacology, 1992Co-Authors: Wongwiwat Tassaneeyakul, Maurice E Veronese, C J Doecke, Michael E Mcmanus, Donald J. Birkett, Lloyd Sansom, John O MinersAbstract:1. The disposition of phenytoin and Tolbutamide was compared in eighteen healthy young adults separately administered single therapeutic doses (sodium phenytoin 300 mg, Tolbutamide 500 mg) of the two drugs. 2. Within the group, ratios of ranges of total and unbound areas under the plasma concentration-time curves were similar for both drugs. 3. There were significant (P < 0.001) correlations between total (r = 0.88) and unbound (r = 0.86) areas under the plasma phenytoin and Tolbutamide concentration-time curves. 4. The results are consistent with the involvement of the same cytochrome P-450 isoenzyme(s) in the metabolism of Tolbutamide and phenytoin.
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relationship between phenytoin and Tolbutamide hydroxylations in human liver microsomes
British Journal of Clinical Pharmacology, 1991Co-Authors: C J Doecke, Maurice E Veronese, John O Miners, D J Birkett, S M Pond, L N Sansom, Michael E McmanusAbstract:1. The metabolic interaction of phenytoin and Tolbutamide in human liver microsomes was investigated. 2. Phenytoin 4-hydroxylation (mean Km 29.6 microM, n = 3) was competitively inhibited by Tolbutamide (mean Ki 106.2 microM, n = 3) and Tolbutamide methylhydroxylation (mean Km 85.6 microM, n = 3) was competitively inhibited by phenytoin (mean Ki 22.6 microM, n = 3). 3. A significant correlation was obtained between phenytoin and Tolbutamide hydroxylations in microsomes from 18 human livers (rs = 0.82, P less than 0.001). 4. Sulphaphenazole was a potent inhibitor of both phenytoin and Tolbutamide hydroxylations with IC50 values of 0.4 microM and 0.6 microM, respectively. 5. Mephenytoin was a poor inhibitor of both phenytoin and Tolbutamide hydroxylations with IC50 values greater than 400 microM for both reactions. 6. Anti-rabbit P450IIC3 IgG inhibited both phenytoin and Tolbutamide hydroxylations in human liver microsomes by 62 and 68%, respectively. 7. These in vitro studies are consistent with phenytoin 4-hydroxylation and Tolbutamide methylhydroxylation being catalysed by the same cytochrome P450 isozyme(s) in human liver microsomes.
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validation of the Tolbutamide metabolic ratio for population screening with use of sulfaphenazole to produce model phenotypic poor metabolizers
Clinical Pharmacology & Therapeutics, 1990Co-Authors: Maurice E Veronese, John O Miners, David Randles, Debbie Gregov, D J BirkettAbstract:The present study has validated kinetically a convenient method to measure Tolbutamide hydroxylation capacity in human beings by use of urinary metabolic ratios. The known in vivo and in vitro inhibitory properties of sulfaphenazole were used to convert control phase subjects to phenotypically “poor” metabolizers of Tolbutamide. Six healthy subjects were given a single 500 mg oral dose of Tolbutamide with and without sulfaphenazole, 500 mg every 12 hours. Tolbutamide, hydroxyTolbutamide, and carboxyTolbutamide in urine were determined by newly developed HPLC procedures. Plasma Tolbutamide clearance and half-life were measured, as were the metabolic ratio (hydroxyTolbutamide + carboxyTolbutamide/Tolbutamide) in successive 6-hour urine collections. The mean Tolbutamide plasma clearance decreased from 0.196 ± 0.026 ml/min/kg without sulfaphenazole to 0.039 ± 0.009 ml/min kg with sulfaphenazole, and the mean half-life of Tolbutamide increased from 7.28 ± 0.89 hours to 38.76 ± 13.30 hours. The metabolic ratio determined in the 6 to 12 hour urine collection period decreased from 794.0 ± 86.6 to 126.0 ± 79.3, and this collection period also gave the best separation of subjects between phases. There was a good correlation between Tolbutamide plasma clearance and metabolic ratio (rs = 0.853, p < 0.01, n = 12) and between the percentage decrease in plasma Tolbutamide clearance and the percentage decrease in metabolic ratio (r = 0.932, p < 0.01, n = 6). The Tolbutamide urinary metabolic ratio therefore effectively distinguishes Tolbutamide hydroxylase activity in “normal” subjects and in those converted to model phenotypically “poor” metabolizers by sulfaphenazole. Clinical Pharmacology and Therapeutics (1990) 47, 403–411; doi:10.1038/clpt.1990.46
D J Birkett - One of the best experts on this subject based on the ideXlab platform.
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relationship between phenytoin and Tolbutamide hydroxylations in human liver microsomes
British Journal of Clinical Pharmacology, 1991Co-Authors: C J Doecke, Maurice E Veronese, John O Miners, D J Birkett, S M Pond, L N Sansom, Michael E McmanusAbstract:1. The metabolic interaction of phenytoin and Tolbutamide in human liver microsomes was investigated. 2. Phenytoin 4-hydroxylation (mean Km 29.6 microM, n = 3) was competitively inhibited by Tolbutamide (mean Ki 106.2 microM, n = 3) and Tolbutamide methylhydroxylation (mean Km 85.6 microM, n = 3) was competitively inhibited by phenytoin (mean Ki 22.6 microM, n = 3). 3. A significant correlation was obtained between phenytoin and Tolbutamide hydroxylations in microsomes from 18 human livers (rs = 0.82, P less than 0.001). 4. Sulphaphenazole was a potent inhibitor of both phenytoin and Tolbutamide hydroxylations with IC50 values of 0.4 microM and 0.6 microM, respectively. 5. Mephenytoin was a poor inhibitor of both phenytoin and Tolbutamide hydroxylations with IC50 values greater than 400 microM for both reactions. 6. Anti-rabbit P450IIC3 IgG inhibited both phenytoin and Tolbutamide hydroxylations in human liver microsomes by 62 and 68%, respectively. 7. These in vitro studies are consistent with phenytoin 4-hydroxylation and Tolbutamide methylhydroxylation being catalysed by the same cytochrome P450 isozyme(s) in human liver microsomes.
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validation of the Tolbutamide metabolic ratio for population screening with use of sulfaphenazole to produce model phenotypic poor metabolizers
Clinical Pharmacology & Therapeutics, 1990Co-Authors: Maurice E Veronese, John O Miners, David Randles, Debbie Gregov, D J BirkettAbstract:The present study has validated kinetically a convenient method to measure Tolbutamide hydroxylation capacity in human beings by use of urinary metabolic ratios. The known in vivo and in vitro inhibitory properties of sulfaphenazole were used to convert control phase subjects to phenotypically “poor” metabolizers of Tolbutamide. Six healthy subjects were given a single 500 mg oral dose of Tolbutamide with and without sulfaphenazole, 500 mg every 12 hours. Tolbutamide, hydroxyTolbutamide, and carboxyTolbutamide in urine were determined by newly developed HPLC procedures. Plasma Tolbutamide clearance and half-life were measured, as were the metabolic ratio (hydroxyTolbutamide + carboxyTolbutamide/Tolbutamide) in successive 6-hour urine collections. The mean Tolbutamide plasma clearance decreased from 0.196 ± 0.026 ml/min/kg without sulfaphenazole to 0.039 ± 0.009 ml/min kg with sulfaphenazole, and the mean half-life of Tolbutamide increased from 7.28 ± 0.89 hours to 38.76 ± 13.30 hours. The metabolic ratio determined in the 6 to 12 hour urine collection period decreased from 794.0 ± 86.6 to 126.0 ± 79.3, and this collection period also gave the best separation of subjects between phases. There was a good correlation between Tolbutamide plasma clearance and metabolic ratio (rs = 0.853, p < 0.01, n = 12) and between the percentage decrease in plasma Tolbutamide clearance and the percentage decrease in metabolic ratio (r = 0.932, p < 0.01, n = 6). The Tolbutamide urinary metabolic ratio therefore effectively distinguishes Tolbutamide hydroxylase activity in “normal” subjects and in those converted to model phenotypically “poor” metabolizers by sulfaphenazole. Clinical Pharmacology and Therapeutics (1990) 47, 403–411; doi:10.1038/clpt.1990.46
