Journal of Clinical Pharmacology最新文献_第7页

Pilot evaluation of the population pharmacokinetics of bumetanide in term newborn infants with seizures. 布美他尼对足月新生儿癫痫发作人群药代动力学的初步评价。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2016-03-01 Epub Date: 2015-09-14 DOI: 10.1002/jcph.596

Vincent Jullien, Ronit M Pressler, Geraldine Boylan, Mats Blennow, Neil Marlow, Catherine Chiron, Gerard Pons

{"title":"Pilot evaluation of the population pharmacokinetics of bumetanide in term newborn infants with seizures.","authors":"Vincent Jullien, Ronit M Pressler, Geraldine Boylan, Mats Blennow, Neil Marlow, Catherine Chiron, Gerard Pons","doi":"10.1002/jcph.596","DOIUrl":"https://doi.org/10.1002/jcph.596","url":null,"abstract":"Recent experimental data suggest bumetanide as a possible therapeutic option in newborn infants with seizures after birth asphyxia. Because pharmacokinetic (PK) data are lacking in this population, who very often benefit from therapeutic cooling, which can modify the PK behavior of a drug, a PK study was conducted in term infants with seizures caused by hypoxic-ischemic encephalopathy. Fourteen infants were included, 13 of them being cooled. Forty-nine blood samples were available for the determination of the plasma concentration of bumetanide. Concentration-time data were analyzed by the use of a population approach performed with Monolix Software. Bumetanide was found to follow a 2-compartment model. The mean values were 0.063 L/h for clearance, 0.28 and 0.44 L for the central and peripheral distribution volumes, respectively, and 0.59 L/h for the distribution clearance. Birth body weight explained the interindividual variability of bumetanide clearance via an allometric model. No relationship was found between bumetanide exposure and its efficacy (reduction in seizure burden) or its toxicity (hearing loss). This study describes the first PK model of bumetanide in hypothermia-treated infants with seizures. ","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"56 3","pages":"284-90"},"PeriodicalIF":2.9,"publicationDate":"2016-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.596","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34019788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

A phase-1, open-label, single-dose study of the pharmacokinetics of buparlisib in subjects with mild to severe hepatic impairment. 布帕利西布在轻度至重度肝功能损害患者中的1期、开放标签、单剂量药代动力学研究。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2016-03-01 Epub Date: 2015-09-14 DOI: 10.1002/jcph.590

Denes Csonka, Katharine Hazell, Edward Waldron, Sebastien Lorenzo, Vincent Duval, Lucia Trandafir, Zhanna D Kobalava

{"title":"A phase-1, open-label, single-dose study of the pharmacokinetics of buparlisib in subjects with mild to severe hepatic impairment.","authors":"Denes Csonka, Katharine Hazell, Edward Waldron, Sebastien Lorenzo, Vincent Duval, Lucia Trandafir, Zhanna D Kobalava","doi":"10.1002/jcph.590","DOIUrl":"https://doi.org/10.1002/jcph.590","url":null,"abstract":"The pharmacokinetics (PK) and safety of single-dose buparlisib (30 mg) were assessed in subjects with mild to severe hepatic impairment (n = 6 each) relative to healthy controls (n = 13). Blood samples were collected until 336 hours postdose and evaluated by liquid chromatography tandem mass spectrometry. PK parameters (including area under the curve [AUC∞ ] and Cmax ) were derived using noncompartmental analysis. Buparlisib was rapidly absorbed in all groups (median Tmax 1.0-1.3 h). Buparlisib exposure (AUC∞ ) was moderately increased in subjects with mild (geometric mean ratio [GMR] 1.16; 90%CI 0.81, 1.65), moderate (GMR 1.14; 90%CI 0.80, 1.63), or severe (GMR 1.20; 90%CI 0.84, 1.72) hepatic impairment, relative to healthy controls. Apparent oral clearance was similar across groups. Due to a higher unbound fraction in the severe group (0.21) than all other groups (0.17), subjects with severe hepatic impairment had greater exposure to unbound buparlisib (GMR relative to healthy controls: AUC∞ 1.52; 90%CI 1.09, 2.13; Cmax 1.83; 90%CI 1.42, 2.36). The results indicate that a buparlisib dose adjustment may not be necessary for patients with mild to moderate hepatic impairment. The safety and therapeutic indices should be considered before determining if a dose adjustment is appropriate for patients with severe hepatic impairment. ","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"56 3","pages":"316-23"},"PeriodicalIF":2.9,"publicationDate":"2016-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.590","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33912471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Doxylamine pharmacokinetics following single dose oral administration in children ages 2-17 years. 2-17岁儿童单次口服多西胺的药代动力学。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2013-11-01 Epub Date: 2013-07-18 DOI: 10.1002/jcph.137

Guhan Balan, Gary A Thompson, Roger Gibb, Lijuan Li, David Hull, Molly Seeck

{"title":"Doxylamine pharmacokinetics following single dose oral administration in children ages 2-17 years.","authors":"Guhan Balan, Gary A Thompson, Roger Gibb, Lijuan Li, David Hull, Molly Seeck","doi":"10.1002/jcph.137","DOIUrl":"https://doi.org/10.1002/jcph.137","url":null,"abstract":"To characterize doxylamine pharmacokinetics in children. This study was conducted in 41 subjects, ages 2-17 years. Doxylamine succinate doses based on age/weight ranged from 3.125 to 12.5 mg. A single oral dose was administered with 2 to 4 oz. of water or decaffeinated beverages ∼2 hours after a light breakfast. Plasma samples were obtained before and for 72 hours after dosing and analyzed for doxylamine using HPLC MS/MS. Pharmacokinetic parameters were estimated using non-compartmental methods and relationships with age were assessed using linear regression. Over the fourfold dose range, Cmax was similar while AUC increased only 60%, although not statistically significant (P-value = 0.0517). As expected due to increasing body size, CLo and Vz /F increased with age. Due to a similar increase with age for Clo and Vz /F, no age-related differences in t1/2,z were observed (∼16 hours). Allometric scaling indicated no maturation related changes in CLo ; although Vz /F remained age-dependent, the predicted range decreased ∼70%. Overall, the single doses were well tolerated. Somnolence was the most common reported AE with no apparent differences in incidence noted with age. An age/weight dosing nomogram utilizing a fourfold range of doses achieves similar Cmax , whereas AUC increases only 60%. ","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"53 11","pages":"1177-85"},"PeriodicalIF":2.9,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31235886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

Impact of donor and recipient CYP3A5 and ABCB1 genetic polymorphisms on tacrolimus dosage requirements and rejection in Caucasian Spanish liver transplant patients. 供体和受体CYP3A5和ABCB1基因多态性对西班牙白种肝移植患者他克莫司剂量需求和排斥反应的影响

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2013-11-01 Epub Date: 2013-09-11 DOI: 10.1002/jcph.154

Miguel Angel Gómez-Bravo, Magdalena Salcedo, Constantino Fondevila, Francisco Suarez, José Castellote, Sebastián Rufian, José Antonio Pons, José María Alamo, Olga Millán, Mercè Brunet

{"title":"Impact of donor and recipient CYP3A5 and ABCB1 genetic polymorphisms on tacrolimus dosage requirements and rejection in Caucasian Spanish liver transplant patients.","authors":"Miguel Angel Gómez-Bravo, Magdalena Salcedo, Constantino Fondevila, Francisco Suarez, José Castellote, Sebastián Rufian, José Antonio Pons, José María Alamo, Olga Millán, Mercè Brunet","doi":"10.1002/jcph.154","DOIUrl":"https://doi.org/10.1002/jcph.154","url":null,"abstract":"Studies of liver transplant (LT) patients, mainly in Asians, have evaluated the influence of the CYP3A5*1 allele and P-glycoprotein gene ABCB1 on tacrolimus pharmacokinetics or biopsy-proven acute rejection (BPAR) incidence, with no conclusive results. To investigate these issues, 98 Caucasian Spanish LT patients with tacrolimus, mycophenolate mofetil and steroids and 88 cadaveric donors were genotyped for the SNPs CYP3A5 6986G>A, ABCB1 1236C>T, ABCB1 2677G>A/T and ABCB1 3435C>T;. On day 7 post-LT, patients with a native CYP3A5*1 allele had significantly lower tacrolimus trough concentrations C0 (P = .03) and dose-adjusted concentrations C0 /D (P = .02) than CYP3A5 *3/*3 homozygotes. Three months post-LT, patients carrying a liver with CYP3A5*1 had significantly lower C0 /D (P = .03) and took significantly higher tacrolimus doses (P = .03) than the corresponding *3/*3 homozygotes. ABCB1 SNPs showed no significant association with tacrolimus variables. The 3-month incidence of BPAR was 10.2%, with no statistically significant differences related to CYP3A5 (14.3% in expresser vs. 9.5% in non-expresser) or ABCB1 genotype of either patient or donor. We conclude that in Caucasian Spanish LT patients, a native or graft-borne CYP3A5*1 allele tends to lower tacrolimus concentrations and increase dosage needs, but has no significant impact on the incidence of BPAR. ","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"53 11","pages":"1146-54"},"PeriodicalIF":2.9,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31261016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 27

Pharmacokinetics and pharmacodynamics of vincristine sulfate liposome injection (VSLI) in adults with acute lymphoblastic leukemia. 硫酸长春新碱脂质体注射液(VSLI)在成人急性淋巴细胞白血病中的药代动力学和药效学。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2013-11-01 Epub Date: 2013-08-17 DOI: 10.1002/jcph.155

Jeffrey A Silverman, Laurie Reynolds, Steven R Deitcher

{"title":"Pharmacokinetics and pharmacodynamics of vincristine sulfate liposome injection (VSLI) in adults with acute lymphoblastic leukemia.","authors":"Jeffrey A Silverman, Laurie Reynolds, Steven R Deitcher","doi":"10.1002/jcph.155","DOIUrl":"https://doi.org/10.1002/jcph.155","url":null,"abstract":"Vincristine sulfate liposome injection (VSLI,) is a sphingomyelin and cholesterol nanoparticle formulation of vincristine sulfate (VCR) that was designed to overcome the dosing and pharmacokinetic limitations of standard VCR. In contrast to the rapid CL and wide tissue distribution of non-liposomal VCR, VSLI circulates in plasma for a prolonged period of time, with a slow CL of 345 mL/h and relatively small Vd of 3,570 mL. This facilitates enhanced and prolonged tumor-tissue delivery of VCR. The maximum tolerated dose of VSLI, 2.25 mg/m(2) once per week without a dose cap, enables individual and cumulative VCR exposure unachievable with non-liposomal VCR at its labeled dose of 1.4 mg/m(2) . VSLI is associated with a dose-dependent peripheral neurotoxicity albeit at doses that are two to three times that of standard VCR. VCR dose intensification with VSLI correlated with an increased probability of overall response and a strong trend towards increased complete response in adults with relapsed and/or refractory acute lymphoblastic leukemia. Overall, VSLI improves the therapeutic index by facilitating increased dose intensification while maintaining a predictable and manageable safety profile. ","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"53 11","pages":"1139-45"},"PeriodicalIF":2.9,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31626029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 35

Co-medication of pravastatin and paroxetine-a categorical study. 普伐他汀与帕罗西汀联合用药的分类研究。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2013-11-01 Epub Date: 2013-08-13 DOI: 10.1002/jcph.151

Li An, Priyadarshini P Ravindran, Swetha Renukunta, Srinivas Denduluri

{"title":"Co-medication of pravastatin and paroxetine-a categorical study.","authors":"Li An, Priyadarshini P Ravindran, Swetha Renukunta, Srinivas Denduluri","doi":"10.1002/jcph.151","DOIUrl":"https://doi.org/10.1002/jcph.151","url":null,"abstract":"Electronic Medical Records (EMRs) are wealthy storehouses of patient information, to which data mining techniques can be prudently applied to reveal clinically significant patterns. Detecting patterns in drug-drug interactions, leading to adverse drug reactions is a powerful application of EMR data mining. Adverse effects of drug treatments can be investigated by mining clinical laboratory tests data which are reliable indicators of abnormal physiological functions. We report here the co-medication effects of pravastatin (HMG-CoA reductase inhibitor) and paroxetine (selective serotonin reuptake inhibitor (SSRI) anti-depressant) on significant clinical parameters, identified through a data mining analysis conducted on the Allscripts data warehouse. We found that the concomitant drug treatments of pravastatin and paroxetine increased the mean values of glucose serum from 113.2 to 132.1 mg/dL and international normalized ratio (INR) from 2.18 to 2.52, respectively. It also decreased the mean values of estimated glomerular filtration rate (eGFR) from 43 to 37 mL/min/1.73 m(3) and blood CO2 levels from 24.8 to 23.9 mEq/L respectively. Our findings indicate that co-medication of pravastatin and paroxetine might have significant impact on blood anti-coagulation, kidney function, and glucose homeostasis. Our methodology can be applied to any EMR data set to reveal co-medication effects of any drug pairs. ","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"53 11","pages":"1212-9"},"PeriodicalIF":2.9,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.151","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31626443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

Safety, tolerability, and pharmacokinetics of oral and intravenous administration of GSK1322322, a peptide deformylase inhibitor. 肽去甲酰基酶抑制剂GSK1322322口服和静脉给药的安全性、耐受性和药代动力学

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2013-11-01 Epub Date: 2013-08-13 DOI: 10.1002/jcph.150

Odin J Naderer, Lori S Jones, John Zhu, Milena Kurtinecz, Etienne Dumont

{"title":"Safety, tolerability, and pharmacokinetics of oral and intravenous administration of GSK1322322, a peptide deformylase inhibitor.","authors":"Odin J Naderer, Lori S Jones, John Zhu, Milena Kurtinecz, Etienne Dumont","doi":"10.1002/jcph.150","DOIUrl":"https://doi.org/10.1002/jcph.150","url":null,"abstract":"GSK1322322 is the first in a new class of antibiotics that targets peptide deformylase (PDF), an essential bacterial enzyme required for protein maturation. This randomized, double-blind, placebo-controlled, eight-cohort phase I trial enrolled 62 healthy volunteers to assess safety, tolerability, and pharmacokinetic profiles of GSK1322322. GSK1322322 was administered as a single oral or intravenous (IV) dose, escalating from 500 to 3,000 mg or repeat IV doses escalating from 500 to 1,500 mg twice daily. Upon repeat IV administration, GSK1322322 exhibits linear pharmacokinetics over time upon repeat doses as shown by time-invariant pharmacokinetics. A dose-proportional increase in area under concentration-time curve was observed after single or repeat IV dosing, whereas clearance at steady state remained generally unchanged across doses. There was minimal accumulation of GSK1322322 after repeat IV twice-daily administration. After oral tablet doses of GSK1322322 1,000 and 1,500 mg, absolute bioavailability was 69% and 56%, respectively. GSK1322322 administration at single and repeat IV doses and at supratherapeutic single IV doses of 2,000 and 3,000 mg was associated with mild-to-moderate drug-related adverse events. On the basis of the pharmacokinetics and tolerability demonstrated in this study, GSK1322322 has the potential to become the first-in-class PDF inhibitor for clinical use. ","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"53 11","pages":"1168-76"},"PeriodicalIF":2.9,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31625712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15

CYP3A-mediated drug-drug interaction potential and excretion of brentuximab vedotin, an antibody-drug conjugate, in patients with CD30-positive hematologic malignancies. cyp3a介导的药物-药物相互作用潜力和brentuximab vedotin(一种抗体-药物偶联物)在cd30阳性血液恶性肿瘤患者中的排泄

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2013-08-01 Epub Date: 2013-06-10 DOI: 10.1002/jcph.116

Tae H Han, Ajay K Gopal, Radhakrishnan Ramchandren, Andre Goy, Robert Chen, Jeffrey V Matous, Maureen Cooper, Laurie E Grove, Stephen C Alley, Carmel M Lynch, Owen A O'Connor

{"title":"CYP3A-mediated drug-drug interaction potential and excretion of brentuximab vedotin, an antibody-drug conjugate, in patients with CD30-positive hematologic malignancies.","authors":"Tae H Han, Ajay K Gopal, Radhakrishnan Ramchandren, Andre Goy, Robert Chen, Jeffrey V Matous, Maureen Cooper, Laurie E Grove, Stephen C Alley, Carmel M Lynch, Owen A O'Connor","doi":"10.1002/jcph.116","DOIUrl":"https://doi.org/10.1002/jcph.116","url":null,"abstract":"Brentuximab vedotin is an antibody-drug conjugate (ADC) that selectively delivers monomethyl auristatin E (MMAE) into CD30-expressing cells. This study evaluated the CYP3A-mediated drug-drug interaction potential of brentuximab vedotin and the excretion of MMAE. Two 21-day cycles of brentuximab vedotin (1.2 or 1.8 mg/kg intravenously) were administered to 56 patients with CD30-positive hematologic malignancies. Each patient also received either a sensitive CYP3A substrate (midazolam), an effective inducer (rifampin), or a strong inhibitor (ketoconazole). Brentuximab vedotin did not affect midazolam exposures. ADC exposures were unaffected by concomitant rifampin or ketoconazole; however, MMAE exposures were lower with rifampin and higher with ketoconazole. The short-term safety profile of brentuximab vedotin in this study was generally consistent with historic clinical observations. The most common adverse events were nausea, fatigue, diarrhea, headache, pyrexia, and neutropenia. Over a 1-week period, ∼23.5% of intact MMAE was recovered after administration of brentuximab vedotin; all other species were below the limit of quantitation. The primary excretion route is via feces (median 72% of the recovered MMAE). These results suggest that brentuximab vedotin (1.8 mg/kg) and MMAE are neither inhibitors nor inducers of CYP3A; however, MMAE is a substrate of CYP3A.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"53 8","pages":"866-77"},"PeriodicalIF":2.9,"publicationDate":"2013-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31496077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 59

Cancer cachexia raises the plasma concentration of oxymorphone through the reduction of CYP3A but not CYP2D6 in oxycodone-treated patients. 在羟考酮治疗的患者中，癌症恶病质通过降低CYP3A而不是CYP2D6来提高氧吗啡酮的血浆浓度。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2013-08-01 Epub Date: 2013-06-03 DOI: 10.1002/jcph.112

Takafumi Naito, Masaki Tashiro, Takuya Ishida, Kazunori Ohnishi, Junichi Kawakami

{"title":"Cancer cachexia raises the plasma concentration of oxymorphone through the reduction of CYP3A but not CYP2D6 in oxycodone-treated patients.","authors":"Takafumi Naito, Masaki Tashiro, Takuya Ishida, Kazunori Ohnishi, Junichi Kawakami","doi":"10.1002/jcph.112","DOIUrl":"https://doi.org/10.1002/jcph.112","url":null,"abstract":"This study evaluated the plasma concentrations of oxycodone and its demethylates and opioid-induced adverse effects based on cachexia stage in cancer patients receiving oxycodone. Seventy patients receiving oxycodone for cancer pain were enrolled. Cachexia was evaluated using the Glasgow Prognostic Score (GPS). Predose plasma concentrations of oxycodone, oxymorphone, and noroxycodone were determined at the titration dose. Opioid-induced adverse effects were monitored for 2 weeks after the titration. Plasma concentrations of oxycodone and oxymorphone but not noroxycodone in patients with a GPS of 2 were significantly higher than that with a GPS of 0. The metabolic ratios of noroxycodone but not oxymorphone to oxycodone in patients with a GPS of 1 and 2 were significantly lower than in those with a GPS of 0. A higher GPS was associated with a higher incidence of somnolence, while the GPS did not affect the incidence of vomiting. Plasma concentrations of oxycodone and oxymorphone were not associated with the incidence of adverse effects. In conclusion, cancer cachexia raised the plasma exposures of oxycodone and oxymorphone through the reduction of CYP3A but not CYP2D6. Although the cachexia elevated the incidence of somnolence, alterations in their pharmacokinetics were not associated with the incidence. ","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"53 8","pages":"812-8"},"PeriodicalIF":2.9,"publicationDate":"2013-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31480079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

Impact of food and different meal types on the pharmacokinetics of rilpivirine. 食物及不同膳食类型对利匹韦林药代动力学的影响。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2013-08-01 Epub Date: 2013-05-30 DOI: 10.1002/jcph.107

Herta M Crauwels, Rolf P G van Heeswijk, Annemie Buelens, Marita Stevens, Katia Boven, Richard M W Hoetelmans

{"title":"Impact of food and different meal types on the pharmacokinetics of rilpivirine.","authors":"Herta M Crauwels, Rolf P G van Heeswijk, Annemie Buelens, Marita Stevens, Katia Boven, Richard M W Hoetelmans","doi":"10.1002/jcph.107","DOIUrl":"https://doi.org/10.1002/jcph.107","url":null,"abstract":"The objective of the study was to determine the impact of food and different meal types on the pharmacokinetics of rilpivirine, a nonnucleoside reverse transcriptase inhibitor. In this open-label, randomized, crossover study, healthy volunteers received a single, oral 75 mg dose of rilpivirine either with a normal-fat breakfast (reference), under fasting conditions, with a high-fat breakfast, or with a protein-rich nutritional drink. Pharmacokinetic parameters were determined by non-compartmental methods and analyzed using a linear mixed-effects model. Safety was assessed throughout. The least-squares mean ratio for area under the plasma concentration-time curve to last timepoint was 0.57 (90% confidence interval [CI]: 0.46-0.72) under fasting conditions compared to dosing with a normal-fat breakfast. With a high-fat breakfast or only a protein-rich nutritional drink, the corresponding values were 0.92 (90% CI: 0.80-1.07) and 0.50 (90% CI: 0.41-0.61), respectively, compared to dosing with a normal-fat breakfast. Under all conditions, rilpivirine was generally safe and well tolerated. Administration of rilpivirine under fasting conditions or with only a protein-rich nutritional drink substantially lowered the oral bioavailability when compared to administration with a normal-fat breakfast. Rilpivirine bioavailability was similar when administered with a high-fat or normal-fat breakfast. Rilpivirine should always be taken with a meal to ensure adequate bioavailability.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"53 8","pages":"834-40"},"PeriodicalIF":2.9,"publicationDate":"2013-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31467269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 46