Assessment of CYP-Mediated Drug Interactions for Enasidenib Based on a Cocktail Study in Patients with Relapse or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
J Clin Pharmacol. 2024 Apr 2. doi: 10.1002/jcph.2436. Online ahead of print.ABSTRACTAs a selective and potent inhibitor targeting the isocitrate dehydrogenase-2 (IDH2) mutant protein, enasidenib obtained approval from the US Food and Drug Administration (FDA) in 2017 for adult patients with acute myeloid leukemia (AML) with an IDH2 mutation. In vitro investigations demonstrated that enasidenib affects various drug metabolic enzymes and transporters. This current investigation aimed to assess enasidenib on the pharmacokinetics (PKs) of CYP substrates, including dextromethorphan (CYP2D6 probe drug), flurbiprofen (CYP2C9 prob...
Source: The Journal of Clinical Pharmacology - April 2, 2024 Category: Drugs & Pharmacology Authors: Yiming Cheng Xiaomin Wang Atalanta Ghosh Jie Pu Leonidas N Carayannopoulos Yan Li Source Type: research

Assessment of CYP-Mediated Drug Interactions for Enasidenib Based on a Cocktail Study in Patients with Relapse or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
J Clin Pharmacol. 2024 Apr 2. doi: 10.1002/jcph.2436. Online ahead of print.ABSTRACTAs a selective and potent inhibitor targeting the isocitrate dehydrogenase-2 (IDH2) mutant protein, enasidenib obtained approval from the US Food and Drug Administration (FDA) in 2017 for adult patients with acute myeloid leukemia (AML) with an IDH2 mutation. In vitro investigations demonstrated that enasidenib affects various drug metabolic enzymes and transporters. This current investigation aimed to assess enasidenib on the pharmacokinetics (PKs) of CYP substrates, including dextromethorphan (CYP2D6 probe drug), flurbiprofen (CYP2C9 prob...
Source: The Journal of Clinical Pharmacology - April 2, 2024 Category: Drugs & Pharmacology Authors: Yiming Cheng Xiaomin Wang Atalanta Ghosh Jie Pu Leonidas N Carayannopoulos Yan Li Source Type: research

Assessment of CYP-Mediated Drug Interactions for Enasidenib Based on a Cocktail Study in Patients with Relapse or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
J Clin Pharmacol. 2024 Apr 2. doi: 10.1002/jcph.2436. Online ahead of print.ABSTRACTAs a selective and potent inhibitor targeting the isocitrate dehydrogenase-2 (IDH2) mutant protein, enasidenib obtained approval from the US Food and Drug Administration (FDA) in 2017 for adult patients with acute myeloid leukemia (AML) with an IDH2 mutation. In vitro investigations demonstrated that enasidenib affects various drug metabolic enzymes and transporters. This current investigation aimed to assess enasidenib on the pharmacokinetics (PKs) of CYP substrates, including dextromethorphan (CYP2D6 probe drug), flurbiprofen (CYP2C9 prob...
Source: The Journal of Clinical Pharmacology - April 2, 2024 Category: Drugs & Pharmacology Authors: Yiming Cheng Xiaomin Wang Atalanta Ghosh Jie Pu Leonidas N Carayannopoulos Yan Li Source Type: research

Assessment of CYP-Mediated Drug Interactions for Enasidenib Based on a Cocktail Study in Patients with Relapse or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
J Clin Pharmacol. 2024 Apr 2. doi: 10.1002/jcph.2436. Online ahead of print.ABSTRACTAs a selective and potent inhibitor targeting the isocitrate dehydrogenase-2 (IDH2) mutant protein, enasidenib obtained approval from the US Food and Drug Administration (FDA) in 2017 for adult patients with acute myeloid leukemia (AML) with an IDH2 mutation. In vitro investigations demonstrated that enasidenib affects various drug metabolic enzymes and transporters. This current investigation aimed to assess enasidenib on the pharmacokinetics (PKs) of CYP substrates, including dextromethorphan (CYP2D6 probe drug), flurbiprofen (CYP2C9 prob...
Source: The Journal of Clinical Pharmacology - April 2, 2024 Category: Drugs & Pharmacology Authors: Yiming Cheng Xiaomin Wang Atalanta Ghosh Jie Pu Leonidas N Carayannopoulos Yan Li Source Type: research

Assessment of CYP-Mediated Drug Interactions for Enasidenib Based on a Cocktail Study in Patients with Relapse or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
J Clin Pharmacol. 2024 Apr 2. doi: 10.1002/jcph.2436. Online ahead of print.ABSTRACTAs a selective and potent inhibitor targeting the isocitrate dehydrogenase-2 (IDH2) mutant protein, enasidenib obtained approval from the US Food and Drug Administration (FDA) in 2017 for adult patients with acute myeloid leukemia (AML) with an IDH2 mutation. In vitro investigations demonstrated that enasidenib affects various drug metabolic enzymes and transporters. This current investigation aimed to assess enasidenib on the pharmacokinetics (PKs) of CYP substrates, including dextromethorphan (CYP2D6 probe drug), flurbiprofen (CYP2C9 prob...
Source: The Journal of Clinical Pharmacology - April 2, 2024 Category: Drugs & Pharmacology Authors: Yiming Cheng Xiaomin Wang Atalanta Ghosh Jie Pu Leonidas N Carayannopoulos Yan Li Source Type: research

Assessment of CYP-Mediated Drug Interactions for Enasidenib Based on a Cocktail Study in Patients with Relapse or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
J Clin Pharmacol. 2024 Apr 2. doi: 10.1002/jcph.2436. Online ahead of print.ABSTRACTAs a selective and potent inhibitor targeting the isocitrate dehydrogenase-2 (IDH2) mutant protein, enasidenib obtained approval from the US Food and Drug Administration (FDA) in 2017 for adult patients with acute myeloid leukemia (AML) with an IDH2 mutation. In vitro investigations demonstrated that enasidenib affects various drug metabolic enzymes and transporters. This current investigation aimed to assess enasidenib on the pharmacokinetics (PKs) of CYP substrates, including dextromethorphan (CYP2D6 probe drug), flurbiprofen (CYP2C9 prob...
Source: The Journal of Clinical Pharmacology - April 2, 2024 Category: Drugs & Pharmacology Authors: Yiming Cheng Xiaomin Wang Atalanta Ghosh Jie Pu Leonidas N Carayannopoulos Yan Li Source Type: research

Assessment of CYP-Mediated Drug Interactions for Enasidenib Based on a Cocktail Study in Patients with Relapse or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
J Clin Pharmacol. 2024 Apr 2. doi: 10.1002/jcph.2436. Online ahead of print.ABSTRACTAs a selective and potent inhibitor targeting the isocitrate dehydrogenase-2 (IDH2) mutant protein, enasidenib obtained approval from the US Food and Drug Administration (FDA) in 2017 for adult patients with acute myeloid leukemia (AML) with an IDH2 mutation. In vitro investigations demonstrated that enasidenib affects various drug metabolic enzymes and transporters. This current investigation aimed to assess enasidenib on the pharmacokinetics (PKs) of CYP substrates, including dextromethorphan (CYP2D6 probe drug), flurbiprofen (CYP2C9 prob...
Source: The Journal of Clinical Pharmacology - April 2, 2024 Category: Drugs & Pharmacology Authors: Yiming Cheng Xiaomin Wang Atalanta Ghosh Jie Pu Leonidas N Carayannopoulos Yan Li Source Type: research

Using Real-World Data to Externally Evaluate Population Pharmacokinetic Models of Dexmedetomidine in Children and Infants
J Clin Pharmacol. 2024 Mar 28. doi: 10.1002/jcph.2434. Online ahead of print.ABSTRACTDexmedetomidine is a sedative used in both adults and off-label in children with considerable reported pharmacokinetic (PK) interindividual variability affecting drug exposure across populations. Several published models describe the population PKs of dexmedetomidine in neonates, infants, children, and adolescents, though very few have been externally evaluated. A prospective PK dataset of dexmedetomidine plasma concentrations in children and young adults aged 0.01-19.9 years was collected as part of a multicenter opportunistic PK study. A...
Source: The Journal of Clinical Pharmacology - March 28, 2024 Category: Drugs & Pharmacology Authors: Sean McCann Vict ória E Helfer Stephen J Balevic Chi D Hornik Stuart L Goldstein Julie Autmizguine Marisa Meyer Amira Al-Uzri Sarah G Anderson Elizabeth H Payne Sitora Turdalieva Daniel Gonzalez Best Pharmaceuticals for Children Act – Pediatric Trials Source Type: research

Using Real-World Data to Externally Evaluate Population Pharmacokinetic Models of Dexmedetomidine in Children and Infants
J Clin Pharmacol. 2024 Mar 28. doi: 10.1002/jcph.2434. Online ahead of print.ABSTRACTDexmedetomidine is a sedative used in both adults and off-label in children with considerable reported pharmacokinetic (PK) interindividual variability affecting drug exposure across populations. Several published models describe the population PKs of dexmedetomidine in neonates, infants, children, and adolescents, though very few have been externally evaluated. A prospective PK dataset of dexmedetomidine plasma concentrations in children and young adults aged 0.01-19.9 years was collected as part of a multicenter opportunistic PK study. A...
Source: The Journal of Clinical Pharmacology - March 28, 2024 Category: Drugs & Pharmacology Authors: Sean McCann Vict ória E Helfer Stephen J Balevic Chi D Hornik Stuart L Goldstein Julie Autmizguine Marisa Meyer Amira Al-Uzri Sarah G Anderson Elizabeth H Payne Sitora Turdalieva Daniel Gonzalez Best Pharmaceuticals for Children Act – Pediatric Trials Source Type: research

Using Real-World Data to Externally Evaluate Population Pharmacokinetic Models of Dexmedetomidine in Children and Infants
J Clin Pharmacol. 2024 Mar 28. doi: 10.1002/jcph.2434. Online ahead of print.ABSTRACTDexmedetomidine is a sedative used in both adults and off-label in children with considerable reported pharmacokinetic (PK) interindividual variability affecting drug exposure across populations. Several published models describe the population PKs of dexmedetomidine in neonates, infants, children, and adolescents, though very few have been externally evaluated. A prospective PK dataset of dexmedetomidine plasma concentrations in children and young adults aged 0.01-19.9 years was collected as part of a multicenter opportunistic PK study. A...
Source: The Journal of Clinical Pharmacology - March 28, 2024 Category: Drugs & Pharmacology Authors: Sean McCann Vict ória E Helfer Stephen J Balevic Chi D Hornik Stuart L Goldstein Julie Autmizguine Marisa Meyer Amira Al-Uzri Sarah G Anderson Elizabeth H Payne Sitora Turdalieva Daniel Gonzalez Best Pharmaceuticals for Children Act – Pediatric Trials Source Type: research

Using Real-World Data to Externally Evaluate Population Pharmacokinetic Models of Dexmedetomidine in Children and Infants
J Clin Pharmacol. 2024 Mar 28. doi: 10.1002/jcph.2434. Online ahead of print.ABSTRACTDexmedetomidine is a sedative used in both adults and off-label in children with considerable reported pharmacokinetic (PK) interindividual variability affecting drug exposure across populations. Several published models describe the population PKs of dexmedetomidine in neonates, infants, children, and adolescents, though very few have been externally evaluated. A prospective PK dataset of dexmedetomidine plasma concentrations in children and young adults aged 0.01-19.9 years was collected as part of a multicenter opportunistic PK study. A...
Source: The Journal of Clinical Pharmacology - March 28, 2024 Category: Drugs & Pharmacology Authors: Sean McCann Vict ória E Helfer Stephen J Balevic Chi D Hornik Stuart L Goldstein Julie Autmizguine Marisa Meyer Amira Al-Uzri Sarah G Anderson Elizabeth H Payne Sitora Turdalieva Daniel Gonzalez Best Pharmaceuticals for Children Act – Pediatric Trials Source Type: research

Effect of Hepatic Impairment on the Pharmacokinetics of Fenfluramine and Norfenfluramine
J Clin Pharmacol. 2024 Mar 25. doi: 10.1002/jcph.2431. Online ahead of print.ABSTRACTFenfluramine (Fintepla®) is approved for the treatment of seizures associated with the rare epileptic encephalopathies Dravet syndrome and Lennox-Gastaut syndrome. Fenfluramine is extensively metabolized; thus, patients with hepatic impairment (HI) might experience changes in exposure to fenfluramine or its metabolites. In this phase 1 study, we investigated the pharmacokinetics (PK) and safety of a single oral dose of 0.35 mg/kg fenfluramine in subjects with mild (n = 8), moderate (n = 8), or severe (n = 7) HI (Child-Pugh A/B/C, respecti...
Source: The Journal of Clinical Pharmacology - March 25, 2024 Category: Drugs & Pharmacology Authors: Aravind Mittur Ryan Madanick Melanie Langlois Brooks Boyd Source Type: research

Effect of Hepatic Impairment on the Pharmacokinetics of Fenfluramine and Norfenfluramine
J Clin Pharmacol. 2024 Mar 25. doi: 10.1002/jcph.2431. Online ahead of print.ABSTRACTFenfluramine (Fintepla®) is approved for the treatment of seizures associated with the rare epileptic encephalopathies Dravet syndrome and Lennox-Gastaut syndrome. Fenfluramine is extensively metabolized; thus, patients with hepatic impairment (HI) might experience changes in exposure to fenfluramine or its metabolites. In this phase 1 study, we investigated the pharmacokinetics (PK) and safety of a single oral dose of 0.35 mg/kg fenfluramine in subjects with mild (n = 8), moderate (n = 8), or severe (n = 7) HI (Child-Pugh A/B/C, respecti...
Source: The Journal of Clinical Pharmacology - March 25, 2024 Category: Drugs & Pharmacology Authors: Aravind Mittur Ryan Madanick Melanie Langlois Brooks Boyd Source Type: research

Effect of Hepatic Impairment on the Pharmacokinetics of Fenfluramine and Norfenfluramine
J Clin Pharmacol. 2024 Mar 25. doi: 10.1002/jcph.2431. Online ahead of print.ABSTRACTFenfluramine (Fintepla®) is approved for the treatment of seizures associated with the rare epileptic encephalopathies Dravet syndrome and Lennox-Gastaut syndrome. Fenfluramine is extensively metabolized; thus, patients with hepatic impairment (HI) might experience changes in exposure to fenfluramine or its metabolites. In this phase 1 study, we investigated the pharmacokinetics (PK) and safety of a single oral dose of 0.35 mg/kg fenfluramine in subjects with mild (n = 8), moderate (n = 8), or severe (n = 7) HI (Child-Pugh A/B/C, respecti...
Source: The Journal of Clinical Pharmacology - March 25, 2024 Category: Drugs & Pharmacology Authors: Aravind Mittur Ryan Madanick Melanie Langlois Brooks Boyd Source Type: research

Pharmacokinetics and Safety of Firsocostat, an Acetyl-Coenzyme A Carboxylase Inhibitor, in Participants with Mild, Moderate, and Severe Hepatic Impairment
J Clin Pharmacol. 2024 Mar 22. doi: 10.1002/jcph.2427. Online ahead of print.ABSTRACTFirsocostat is an oral, liver-targeted inhibitor of acetyl-coenzyme A carboxylase in development for the treatment of metabolic dysfunction-associated steatohepatitis. Hepatic organic anion transporting polypeptides play a significant role in the disposition of firsocostat with minimal contributions from uridine diphospho-glucuronosyltransferase and cytochrome P450 3A enzymes. This phase 1 study evaluated the pharmacokinetics and safety of firsocostat in participants with mild, moderate, or severe hepatic impairment. Participants with stab...
Source: The Journal of Clinical Pharmacology - March 23, 2024 Category: Drugs & Pharmacology Authors: Islam R Younis Cara Nelson Elijah J Weber Ann R Qin Timothy R Watkins Ahmed A Othman Source Type: research