The Experts below are selected from a list of 228 Experts worldwide ranked by ideXlab platform
Kajsa P Kanebratt - One of the best experts on this subject based on the ideXlab platform.
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cytochrome p450 induction by rifampicin in healthy subjects determination using the karolinska cocktail and the endogenous cyp3a4 marker 4β hydroxycholesterol
Clinical Pharmacology & Therapeutics, 2008Co-Authors: Kajsa P Kanebratt, Ulf Diczfalusy, Tobias Backstrom, E Sparve, Eva Bredberg, Ylva Bottiger, Tommy B Andersson, Leif BertilssonAbstract:The Karolinska cocktail, comprising caffeine, losartan, omeprazole, and quinine, was given before and after administration of rifampicin (20, 100, or 500 mg daily) to measure induction of cytochrome P450 (P450) enzymes. Rifampicin was given for 14 days to eight healthy subjects (all of whom possessed at least one wild-type CYP2C9 and one wild-type CYP2C19 gene) in each dose group. 4β-hydroxycholesterol was assessed as an endogenous marker of CYP3A4 induction. A fourfold induction of CYP3A4 was seen at the highest dose by both quinine:3′-hydroxyquinine and 4β-hydroxycholesterol measurements (P < 0.001). CYP3A4 was also induced at the two lower doses of rifampicin when measured by these two markers (P < 0.01 or P < 0.001). CYP1A2, CYP2C9, and CYP2C19 were induced after 500 mg rifampicin daily (1.2-fold, P < 0.05; 1.4-fold, P < 0.05; and 4.2-fold, P < 0.01, respectively). In conclusion, we have shown that the Karolinska cocktail and 4β-hydroxycholesterol can be used for an initial screening of the induction properties of a drug candidate. Clinical Pharmacology & Therapeutics (2008); 84, 5, 589–594 doi:10.1038/clpt.2008.132
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cytochrome p450 induction by rifampicin in healthy subjects determination using the karolinska cocktail and the endogenous cyp3a4 marker 4β hydroxycholesterol
Clinical Pharmacology & Therapeutics, 2008Co-Authors: Kajsa P Kanebratt, Ulf Diczfalusy, Tobias Backstrom, E Sparve, Eva Bredberg, Ylva Bottiger, Tommy Andersson, Leif BertilssonAbstract:The Karolinska cocktail, comprising caffeine, losartan, omeprazole, and quinine, was given before and after administration of rifampicin (20, 100, or 500 mg daily) to measure induction of cytochrome P450 (P450) enzymes. Rifampicin was given for 14 days to eight healthy subjects (all of whom possessed at least one wild-type CYP2C9 and one wild-type CYP2C19 gene) in each dose group. 4beta-hydroxycholesterol was assessed as an endogenous marker of CYP3A4 induction. A fourfold induction of CYP3A4 was seen at the highest dose by both quinine:3'-hydroxyquinine and 4beta-hydroxycholesterol measurements (P < 0.001). CYP3A4 was also induced at the two lower doses of rifampicin when measured by these two markers (P < 0.01 or P < 0.001). CYP1A2, CYP2C9, and CYP2C19 were induced after 500 mg rifampicin daily (1.2-fold, P < 0.05; 1.4-fold, P < 0.05; and 4.2-fold, P < 0.01, respectively). In conclusion, we have shown that the Karolinska cocktail and 4beta-hydroxycholesterol can be used for an initial screening of the induction properties of a drug candidate.
Leif Bertilsson - One of the best experts on this subject based on the ideXlab platform.
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quinine compared to 4β hydroxycholesterol and midazolam as markers for cyp3a induction by rifampicin
Drug Metabolism and Pharmacokinetics, 2014Co-Authors: Linda Bjorkhembergman, Tobias Backstrom, Eva Bredberg, Tommy B Andersson, Leif Bertilsson, Hanna Nylen, Yuko Ronquistnii, Ulf DiczfalusyAbstract:Summary: When developing new drugs appropriate markers for detecting induction and inhibition of cytochrome P450 3A enzymes (CYP3A) are needed. The aim of the present study was to evaluate the quinine/3-hydroxyquinine metabolic ratio (quinine MR) with other suggested markers for CYP3A induction: endogenously formed 4 β -hydroxycholesterol, midazolam clearance in plasma and the 6 β -hydroxycortisol/cortisol ratio in urine. We have previously performed a clinical trial in which 24 healthy subjects were randomized to take 10, 20 or 100 mg daily doses of rifampicin for 14 days ( n = 8 in each group) to achieve a low and moderate CYP3A induction. In newly analyzed data from this study we can show that the quinine MR could detect CYP3A-induction even at the lowest dose of rifampicin (10 mg) (p β -hydroxycholesterol/cholesterol ratio and midazolam clearance. The median fold-induction for the quinine MR compared to baseline was 1.7, 1.8 and 2.6 for the three dosing groups (10, 20 and 100 mg). In conclusion, in this study the quinine MR was comparable to midazolam clearance as a measure of CYP3A activity but easier to determine since only a single blood sample needs to be drawn.
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cytochrome p450 induction by rifampicin in healthy subjects determination using the karolinska cocktail and the endogenous cyp3a4 marker 4β hydroxycholesterol
Clinical Pharmacology & Therapeutics, 2008Co-Authors: Kajsa P Kanebratt, Ulf Diczfalusy, Tobias Backstrom, E Sparve, Eva Bredberg, Ylva Bottiger, Tommy B Andersson, Leif BertilssonAbstract:The Karolinska cocktail, comprising caffeine, losartan, omeprazole, and quinine, was given before and after administration of rifampicin (20, 100, or 500 mg daily) to measure induction of cytochrome P450 (P450) enzymes. Rifampicin was given for 14 days to eight healthy subjects (all of whom possessed at least one wild-type CYP2C9 and one wild-type CYP2C19 gene) in each dose group. 4β-hydroxycholesterol was assessed as an endogenous marker of CYP3A4 induction. A fourfold induction of CYP3A4 was seen at the highest dose by both quinine:3′-hydroxyquinine and 4β-hydroxycholesterol measurements (P < 0.001). CYP3A4 was also induced at the two lower doses of rifampicin when measured by these two markers (P < 0.01 or P < 0.001). CYP1A2, CYP2C9, and CYP2C19 were induced after 500 mg rifampicin daily (1.2-fold, P < 0.05; 1.4-fold, P < 0.05; and 4.2-fold, P < 0.01, respectively). In conclusion, we have shown that the Karolinska cocktail and 4β-hydroxycholesterol can be used for an initial screening of the induction properties of a drug candidate. Clinical Pharmacology & Therapeutics (2008); 84, 5, 589–594 doi:10.1038/clpt.2008.132
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cytochrome p450 induction by rifampicin in healthy subjects determination using the karolinska cocktail and the endogenous cyp3a4 marker 4β hydroxycholesterol
Clinical Pharmacology & Therapeutics, 2008Co-Authors: Kajsa P Kanebratt, Ulf Diczfalusy, Tobias Backstrom, E Sparve, Eva Bredberg, Ylva Bottiger, Tommy Andersson, Leif BertilssonAbstract:The Karolinska cocktail, comprising caffeine, losartan, omeprazole, and quinine, was given before and after administration of rifampicin (20, 100, or 500 mg daily) to measure induction of cytochrome P450 (P450) enzymes. Rifampicin was given for 14 days to eight healthy subjects (all of whom possessed at least one wild-type CYP2C9 and one wild-type CYP2C19 gene) in each dose group. 4beta-hydroxycholesterol was assessed as an endogenous marker of CYP3A4 induction. A fourfold induction of CYP3A4 was seen at the highest dose by both quinine:3'-hydroxyquinine and 4beta-hydroxycholesterol measurements (P < 0.001). CYP3A4 was also induced at the two lower doses of rifampicin when measured by these two markers (P < 0.01 or P < 0.001). CYP1A2, CYP2C9, and CYP2C19 were induced after 500 mg rifampicin daily (1.2-fold, P < 0.05; 1.4-fold, P < 0.05; and 4.2-fold, P < 0.01, respectively). In conclusion, we have shown that the Karolinska cocktail and 4beta-hydroxycholesterol can be used for an initial screening of the induction properties of a drug candidate.
Tommy B Andersson - One of the best experts on this subject based on the ideXlab platform.
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quinine compared to 4β hydroxycholesterol and midazolam as markers for cyp3a induction by rifampicin
Drug Metabolism and Pharmacokinetics, 2014Co-Authors: Linda Bjorkhembergman, Tobias Backstrom, Eva Bredberg, Tommy B Andersson, Leif Bertilsson, Hanna Nylen, Yuko Ronquistnii, Ulf DiczfalusyAbstract:Summary: When developing new drugs appropriate markers for detecting induction and inhibition of cytochrome P450 3A enzymes (CYP3A) are needed. The aim of the present study was to evaluate the quinine/3-hydroxyquinine metabolic ratio (quinine MR) with other suggested markers for CYP3A induction: endogenously formed 4 β -hydroxycholesterol, midazolam clearance in plasma and the 6 β -hydroxycortisol/cortisol ratio in urine. We have previously performed a clinical trial in which 24 healthy subjects were randomized to take 10, 20 or 100 mg daily doses of rifampicin for 14 days ( n = 8 in each group) to achieve a low and moderate CYP3A induction. In newly analyzed data from this study we can show that the quinine MR could detect CYP3A-induction even at the lowest dose of rifampicin (10 mg) (p β -hydroxycholesterol/cholesterol ratio and midazolam clearance. The median fold-induction for the quinine MR compared to baseline was 1.7, 1.8 and 2.6 for the three dosing groups (10, 20 and 100 mg). In conclusion, in this study the quinine MR was comparable to midazolam clearance as a measure of CYP3A activity but easier to determine since only a single blood sample needs to be drawn.
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cytochrome p450 induction by rifampicin in healthy subjects determination using the karolinska cocktail and the endogenous cyp3a4 marker 4β hydroxycholesterol
Clinical Pharmacology & Therapeutics, 2008Co-Authors: Kajsa P Kanebratt, Ulf Diczfalusy, Tobias Backstrom, E Sparve, Eva Bredberg, Ylva Bottiger, Tommy B Andersson, Leif BertilssonAbstract:The Karolinska cocktail, comprising caffeine, losartan, omeprazole, and quinine, was given before and after administration of rifampicin (20, 100, or 500 mg daily) to measure induction of cytochrome P450 (P450) enzymes. Rifampicin was given for 14 days to eight healthy subjects (all of whom possessed at least one wild-type CYP2C9 and one wild-type CYP2C19 gene) in each dose group. 4β-hydroxycholesterol was assessed as an endogenous marker of CYP3A4 induction. A fourfold induction of CYP3A4 was seen at the highest dose by both quinine:3′-hydroxyquinine and 4β-hydroxycholesterol measurements (P < 0.001). CYP3A4 was also induced at the two lower doses of rifampicin when measured by these two markers (P < 0.01 or P < 0.001). CYP1A2, CYP2C9, and CYP2C19 were induced after 500 mg rifampicin daily (1.2-fold, P < 0.05; 1.4-fold, P < 0.05; and 4.2-fold, P < 0.01, respectively). In conclusion, we have shown that the Karolinska cocktail and 4β-hydroxycholesterol can be used for an initial screening of the induction properties of a drug candidate. Clinical Pharmacology & Therapeutics (2008); 84, 5, 589–594 doi:10.1038/clpt.2008.132
Ulf Diczfalusy - One of the best experts on this subject based on the ideXlab platform.
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quinine compared to 4β hydroxycholesterol and midazolam as markers for cyp3a induction by rifampicin
Drug Metabolism and Pharmacokinetics, 2014Co-Authors: Linda Bjorkhembergman, Tobias Backstrom, Eva Bredberg, Tommy B Andersson, Leif Bertilsson, Hanna Nylen, Yuko Ronquistnii, Ulf DiczfalusyAbstract:Summary: When developing new drugs appropriate markers for detecting induction and inhibition of cytochrome P450 3A enzymes (CYP3A) are needed. The aim of the present study was to evaluate the quinine/3-hydroxyquinine metabolic ratio (quinine MR) with other suggested markers for CYP3A induction: endogenously formed 4 β -hydroxycholesterol, midazolam clearance in plasma and the 6 β -hydroxycortisol/cortisol ratio in urine. We have previously performed a clinical trial in which 24 healthy subjects were randomized to take 10, 20 or 100 mg daily doses of rifampicin for 14 days ( n = 8 in each group) to achieve a low and moderate CYP3A induction. In newly analyzed data from this study we can show that the quinine MR could detect CYP3A-induction even at the lowest dose of rifampicin (10 mg) (p β -hydroxycholesterol/cholesterol ratio and midazolam clearance. The median fold-induction for the quinine MR compared to baseline was 1.7, 1.8 and 2.6 for the three dosing groups (10, 20 and 100 mg). In conclusion, in this study the quinine MR was comparable to midazolam clearance as a measure of CYP3A activity but easier to determine since only a single blood sample needs to be drawn.
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cytochrome p450 induction by rifampicin in healthy subjects determination using the karolinska cocktail and the endogenous cyp3a4 marker 4β hydroxycholesterol
Clinical Pharmacology & Therapeutics, 2008Co-Authors: Kajsa P Kanebratt, Ulf Diczfalusy, Tobias Backstrom, E Sparve, Eva Bredberg, Ylva Bottiger, Tommy B Andersson, Leif BertilssonAbstract:The Karolinska cocktail, comprising caffeine, losartan, omeprazole, and quinine, was given before and after administration of rifampicin (20, 100, or 500 mg daily) to measure induction of cytochrome P450 (P450) enzymes. Rifampicin was given for 14 days to eight healthy subjects (all of whom possessed at least one wild-type CYP2C9 and one wild-type CYP2C19 gene) in each dose group. 4β-hydroxycholesterol was assessed as an endogenous marker of CYP3A4 induction. A fourfold induction of CYP3A4 was seen at the highest dose by both quinine:3′-hydroxyquinine and 4β-hydroxycholesterol measurements (P < 0.001). CYP3A4 was also induced at the two lower doses of rifampicin when measured by these two markers (P < 0.01 or P < 0.001). CYP1A2, CYP2C9, and CYP2C19 were induced after 500 mg rifampicin daily (1.2-fold, P < 0.05; 1.4-fold, P < 0.05; and 4.2-fold, P < 0.01, respectively). In conclusion, we have shown that the Karolinska cocktail and 4β-hydroxycholesterol can be used for an initial screening of the induction properties of a drug candidate. Clinical Pharmacology & Therapeutics (2008); 84, 5, 589–594 doi:10.1038/clpt.2008.132
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cytochrome p450 induction by rifampicin in healthy subjects determination using the karolinska cocktail and the endogenous cyp3a4 marker 4β hydroxycholesterol
Clinical Pharmacology & Therapeutics, 2008Co-Authors: Kajsa P Kanebratt, Ulf Diczfalusy, Tobias Backstrom, E Sparve, Eva Bredberg, Ylva Bottiger, Tommy Andersson, Leif BertilssonAbstract:The Karolinska cocktail, comprising caffeine, losartan, omeprazole, and quinine, was given before and after administration of rifampicin (20, 100, or 500 mg daily) to measure induction of cytochrome P450 (P450) enzymes. Rifampicin was given for 14 days to eight healthy subjects (all of whom possessed at least one wild-type CYP2C9 and one wild-type CYP2C19 gene) in each dose group. 4beta-hydroxycholesterol was assessed as an endogenous marker of CYP3A4 induction. A fourfold induction of CYP3A4 was seen at the highest dose by both quinine:3'-hydroxyquinine and 4beta-hydroxycholesterol measurements (P < 0.001). CYP3A4 was also induced at the two lower doses of rifampicin when measured by these two markers (P < 0.01 or P < 0.001). CYP1A2, CYP2C9, and CYP2C19 were induced after 500 mg rifampicin daily (1.2-fold, P < 0.05; 1.4-fold, P < 0.05; and 4.2-fold, P < 0.01, respectively). In conclusion, we have shown that the Karolinska cocktail and 4beta-hydroxycholesterol can be used for an initial screening of the induction properties of a drug candidate.
Tobias Backstrom - One of the best experts on this subject based on the ideXlab platform.
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quinine compared to 4β hydroxycholesterol and midazolam as markers for cyp3a induction by rifampicin
Drug Metabolism and Pharmacokinetics, 2014Co-Authors: Linda Bjorkhembergman, Tobias Backstrom, Eva Bredberg, Tommy B Andersson, Leif Bertilsson, Hanna Nylen, Yuko Ronquistnii, Ulf DiczfalusyAbstract:Summary: When developing new drugs appropriate markers for detecting induction and inhibition of cytochrome P450 3A enzymes (CYP3A) are needed. The aim of the present study was to evaluate the quinine/3-hydroxyquinine metabolic ratio (quinine MR) with other suggested markers for CYP3A induction: endogenously formed 4 β -hydroxycholesterol, midazolam clearance in plasma and the 6 β -hydroxycortisol/cortisol ratio in urine. We have previously performed a clinical trial in which 24 healthy subjects were randomized to take 10, 20 or 100 mg daily doses of rifampicin for 14 days ( n = 8 in each group) to achieve a low and moderate CYP3A induction. In newly analyzed data from this study we can show that the quinine MR could detect CYP3A-induction even at the lowest dose of rifampicin (10 mg) (p β -hydroxycholesterol/cholesterol ratio and midazolam clearance. The median fold-induction for the quinine MR compared to baseline was 1.7, 1.8 and 2.6 for the three dosing groups (10, 20 and 100 mg). In conclusion, in this study the quinine MR was comparable to midazolam clearance as a measure of CYP3A activity but easier to determine since only a single blood sample needs to be drawn.
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cytochrome p450 induction by rifampicin in healthy subjects determination using the karolinska cocktail and the endogenous cyp3a4 marker 4β hydroxycholesterol
Clinical Pharmacology & Therapeutics, 2008Co-Authors: Kajsa P Kanebratt, Ulf Diczfalusy, Tobias Backstrom, E Sparve, Eva Bredberg, Ylva Bottiger, Tommy B Andersson, Leif BertilssonAbstract:The Karolinska cocktail, comprising caffeine, losartan, omeprazole, and quinine, was given before and after administration of rifampicin (20, 100, or 500 mg daily) to measure induction of cytochrome P450 (P450) enzymes. Rifampicin was given for 14 days to eight healthy subjects (all of whom possessed at least one wild-type CYP2C9 and one wild-type CYP2C19 gene) in each dose group. 4β-hydroxycholesterol was assessed as an endogenous marker of CYP3A4 induction. A fourfold induction of CYP3A4 was seen at the highest dose by both quinine:3′-hydroxyquinine and 4β-hydroxycholesterol measurements (P < 0.001). CYP3A4 was also induced at the two lower doses of rifampicin when measured by these two markers (P < 0.01 or P < 0.001). CYP1A2, CYP2C9, and CYP2C19 were induced after 500 mg rifampicin daily (1.2-fold, P < 0.05; 1.4-fold, P < 0.05; and 4.2-fold, P < 0.01, respectively). In conclusion, we have shown that the Karolinska cocktail and 4β-hydroxycholesterol can be used for an initial screening of the induction properties of a drug candidate. Clinical Pharmacology & Therapeutics (2008); 84, 5, 589–594 doi:10.1038/clpt.2008.132
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cytochrome p450 induction by rifampicin in healthy subjects determination using the karolinska cocktail and the endogenous cyp3a4 marker 4β hydroxycholesterol
Clinical Pharmacology & Therapeutics, 2008Co-Authors: Kajsa P Kanebratt, Ulf Diczfalusy, Tobias Backstrom, E Sparve, Eva Bredberg, Ylva Bottiger, Tommy Andersson, Leif BertilssonAbstract:The Karolinska cocktail, comprising caffeine, losartan, omeprazole, and quinine, was given before and after administration of rifampicin (20, 100, or 500 mg daily) to measure induction of cytochrome P450 (P450) enzymes. Rifampicin was given for 14 days to eight healthy subjects (all of whom possessed at least one wild-type CYP2C9 and one wild-type CYP2C19 gene) in each dose group. 4beta-hydroxycholesterol was assessed as an endogenous marker of CYP3A4 induction. A fourfold induction of CYP3A4 was seen at the highest dose by both quinine:3'-hydroxyquinine and 4beta-hydroxycholesterol measurements (P < 0.001). CYP3A4 was also induced at the two lower doses of rifampicin when measured by these two markers (P < 0.01 or P < 0.001). CYP1A2, CYP2C9, and CYP2C19 were induced after 500 mg rifampicin daily (1.2-fold, P < 0.05; 1.4-fold, P < 0.05; and 4.2-fold, P < 0.01, respectively). In conclusion, we have shown that the Karolinska cocktail and 4beta-hydroxycholesterol can be used for an initial screening of the induction properties of a drug candidate.
