PubMed:24517173 JSONTXT

{"project":"maxiaofeng52_800_3","denotations":[{"id":"T1","span":{"begin":13,"end":22},"obj":"CI"},{"id":"T2","span":{"begin":258,"end":267},"obj":"CI"},{"id":"T3","span":{"begin":846,"end":855},"obj":"CI"},{"id":"T4","span":{"begin":1275,"end":1284},"obj":"CI"},{"id":"T5","span":{"begin":1511,"end":1520},"obj":"CI"},{"id":"T6","span":{"begin":1563,"end":1572},"obj":"CI"},{"id":"T7","span":{"begin":1651,"end":1660},"obj":"CI"},{"id":"T8","span":{"begin":1802,"end":1811},"obj":"CI"},{"id":"T9","span":{"begin":359,"end":366},"obj":"CI"}],"text":"Personalized oxycodone dosing: using pharmacogenetic testing and clinical pharmacokinetics to reduce toxicity risk and increase effectiveness.\nOBJECTIVE: To develop a framework for integrating pharmacogenetics with clinical pharmacokinetics for personalized oxycodone dosing based on a patient's CYP2D6 phenotype.\nDESIGN: Randomized, crossover, double-blind, placebo-controlled. Subjects were genotyped as CYP2D6 ultra-rapid metabolizer, extensive metabolizer, or poor metabolizer phenotypes. Five subjects from each phenotype were randomly selected for inclusion in our study.\nSETTING: Studies were performed in silico.\nSUBJECTS: The subjects were male, age 26 years, height 181.2 cm, and weight 76.3 kg. They were healthy without comorbidities, and their medical examinations were normal.\nMETHODS: The trajectories of phenotype-specific plasma oxycodone concentration-time profiles were analyzed using weighted nonlinear least-squares regression with WinSAAM software. A global two-stage population-based model data analysis procedure was used to analyze the studies. Clinical pharmacokinetics were calculated using the R package cpk, eliminating the need to perform hand-calculations.\nRESULTS: Our study shows how clinicians can reduce risk and increase effectiveness for oxycodone dosing by (1) determining the patient's likely metabolic response through testing a patient's CYP2D6 phenotype, and (2) calculating clinical pharmacokinetics specific to the patient's CYP2D6 phenotype to design a personalized oxycodone dosing regimen.\nCONCLUSIONS: Personalized oxycodone dosing is a new tool for a clinician treating chronic pain patients requiring oxycodone. By expressing a patient's CYP2D6 phenotype pharmacokinetically, a clinician (at least theoretically) can improve the safety and efficacy of oxycodone and decrease the risk for iatrogenically induced overdose or death. Pharmacokinomics provides a general framework for the integration of pharmacogenetics with clinical pharmacokinetics into clinical practice for gene-based prescribing."}

{"project":"wangzhuo19_800_3","denotations":[{"id":"T8","span":{"begin":1802,"end":1811},"obj":"CI"},{"id":"T7","span":{"begin":1651,"end":1660},"obj":"CI"},{"id":"T6","span":{"begin":1563,"end":1572},"obj":"CI"},{"id":"T5","span":{"begin":1511,"end":1520},"obj":"CI"},{"id":"T4","span":{"begin":1275,"end":1284},"obj":"CI"},{"id":"T3","span":{"begin":846,"end":855},"obj":"CI"},{"id":"T2","span":{"begin":258,"end":267},"obj":"CI"},{"id":"T1","span":{"begin":13,"end":22},"obj":"CI"},{"id":"T9","span":{"begin":359,"end":366},"obj":"CI"}],"text":"Personalized oxycodone dosing: using pharmacogenetic testing and clinical pharmacokinetics to reduce toxicity risk and increase effectiveness.\nOBJECTIVE: To develop a framework for integrating pharmacogenetics with clinical pharmacokinetics for personalized oxycodone dosing based on a patient's CYP2D6 phenotype.\nDESIGN: Randomized, crossover, double-blind, placebo-controlled. Subjects were genotyped as CYP2D6 ultra-rapid metabolizer, extensive metabolizer, or poor metabolizer phenotypes. Five subjects from each phenotype were randomly selected for inclusion in our study.\nSETTING: Studies were performed in silico.\nSUBJECTS: The subjects were male, age 26 years, height 181.2 cm, and weight 76.3 kg. They were healthy without comorbidities, and their medical examinations were normal.\nMETHODS: The trajectories of phenotype-specific plasma oxycodone concentration-time profiles were analyzed using weighted nonlinear least-squares regression with WinSAAM software. A global two-stage population-based model data analysis procedure was used to analyze the studies. Clinical pharmacokinetics were calculated using the R package cpk, eliminating the need to perform hand-calculations.\nRESULTS: Our study shows how clinicians can reduce risk and increase effectiveness for oxycodone dosing by (1) determining the patient's likely metabolic response through testing a patient's CYP2D6 phenotype, and (2) calculating clinical pharmacokinetics specific to the patient's CYP2D6 phenotype to design a personalized oxycodone dosing regimen.\nCONCLUSIONS: Personalized oxycodone dosing is a new tool for a clinician treating chronic pain patients requiring oxycodone. By expressing a patient's CYP2D6 phenotype pharmacokinetically, a clinician (at least theoretically) can improve the safety and efficacy of oxycodone and decrease the risk for iatrogenically induced overdose or death. Pharmacokinomics provides a general framework for the integration of pharmacogenetics with clinical pharmacokinetics into clinical practice for gene-based prescribing."}