Aprepitant pharmacokinetics and assessing the impact of aprepitant on cyclophosphamide metabolism in cancer patients undergoing hematopoietic stem cell transplantation.

Abstract:

:Aprepitant, a neurokinin antagonist, is an effective antiemetic agent in chemotherapy for delayed nausea and vomiting. The study objective was to evaluate the pharmacokinetics of aprepitant and concurrent cyclophosphamide (CY), often a component of hematopoietic stem cell transplant (HSCT) conditioning regimen, in cancer patients undergoing HSCT. Forty subjects were randomized to either aprepitant or placebo in addition to standard antiemetics. Aprepitant or placebo was started 1 hour before the first chemotherapy or radiation dose for HSCT conditioning and administered daily until 4 days after infusion of the hematopoietic cell graft (for a total of 10-12 days). Serial blood samples were collected for aprepitant and CY plus 2 important CY metabolites. The results indicate that aprepitant is well absorbed and does not auto-induce its metabolism. No significant drug interaction was observed with CY or its metabolites. A significant portion of the patients had subtherapeutic aprepitant concentrations; however, chemotherapy-induced nausea and vomiting were effectively managed. No dosage adjustment was necessary, and administration of aprepitant in HSCT at the prescribed dosage of 125 mg orally on day 1 and 80 mg orally on each consecutive day through day +4 after HSCT was well tolerated with no significant changes in CY pharmacokinetic parameters.

journal_name

J Clin Pharmacol

authors

Bubalo JS,Cherala G,McCune JS,Munar MY,Tse S,Maziarz R

doi

10.1177/0091270011398243

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

586-94

issue

4

eissn

0091-2700

issn

1552-4604

pii

0091270011398243

journal_volume

52

pub_type

杂志文章,随机对照试验
  • The relation of anticonvulsant drug levels to complete seizure control.

    abstract::This study was undertaken to determine the relationship of serum ACD levels to dosage in a group of patients who had been seizure free for at least two years. It demonstrated that some patients remain completely seizure free with DPH and/or phenobarbital serum concentrations which are well below the reported "optimal"...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1002/j.1552-4604.1976.tb01491.x

    authors: Feldman RG,Pippenger CE

    更新日期:1976-01-01 00:00:00

  • Clinical relevance of cannabis tolerance and dependence.

    abstract::Psychoactive drugs are often widely used before tolerance and dependence is fully appreciated. Tolerance to cannabis-induced cardiovascular and autonomic changes, decreased intraocular pressure, sleep and sleep EEG, mood and behavioral changes is acquired and, to a great degree, lost rapidly with optimal conditions. M...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1981.tb02589.x

    authors: Jones RT,Benowitz NL,Herning RI

    更新日期:1981-08-01 00:00:00

  • Effect of Renal Function Impairment on the Pharmacokinetics, Safety, and Tolerability of the Iminosugar Sinbaglustat.

    abstract::Sinbaglustat (ACT-519276), a brain-penetrating inhibitor of glucosylceramide synthase and nonlysosomal glucosylceramidase, is developed as a new therapy for lysosomal storage disorders. In the first-in-human study, sinbaglustat was primarily excreted unchanged in urine. This study was conducted to evaluate the effect ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1808

    authors: Melchior M,Dingemanse J,Alatrach A,Feldkamp T,Sidharta PN,Géhin M

    更新日期:2020-12-23 00:00:00

  • Increased potency of nondepolarizing relaxants after poliomyelitis.

    abstract::The pathophysiology of poliomyelitis and the recognition of the "post-polio syndrome" suggest that susceptibility to muscle relaxants of patients previously affected by this disease, may be altered. We compared the effects of d-tubocurarine (dTc), pancuronium (P), and gallamine (G) on two pediatric surgical patient gr...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1990.tb03458.x

    authors: Gyermek L

    更新日期:1990-02-01 00:00:00

  • A computer-based, problem-solving system of instruction in clinical pharmacology.

    abstract::Advances in microcomputer technology provide new ways of incorporating PBL procedures in clinical pharmacology courses. Developments in graphics-user interfaces and analog/digital systems that display physiologic information directly on the monitor enable the computer to serve as a learning resource as laboratory clas...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1991.tb04962.x

    authors: Hutcheon DE,el-Gawly HW

    更新日期:1991-03-01 00:00:00

  • Extrapolation of Adult Efficacy to Pediatric Patients With Chemotherapy-Induced Nausea and Vomiting.

    abstract::Chemotherapy-induced nausea and vomiting (CINV) is a common treatment-related adverse event that negatively impacts the quality of life of cancer patients. During pediatric drug development, extrapolation of efficacy from adult to pediatric populations is a pathway that can minimize the exposure of children to unneces...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1577

    authors: Momper JD,Heinrichs MT,Krudys K,Griebel D,Kumar S,Kim I,Mehrotra N,Mulberg AE,Garimella N,Nelson R,Reaman G,Sinha V,Yao L,Zineh I,Burckart G,Sachs H,Mulugeta Y

    更新日期:2020-06-01 00:00:00

  • An atypical course of neuroleptic malignant syndrome.

    abstract::Based on the discussion of NMS, certain conclusions may be reached in regard to this patient. In the psychiatric setting, agitation and confusion alone are not suggestive of NMS. However in this patient, the symptoms of agitation, the rapid development of EPS symptoms unresponsive to anticholinergic therapy, autonomic...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1994.tb02001.x

    authors: Schneiderhan ME,Marken PA

    更新日期:1994-04-01 00:00:00

  • Absence of effect of telbivudine on cardiac repolarization: results of a thorough QT/QTc study in healthy participants.

    abstract::The effect of telbivudine on cardiac repolarization was evaluated in healthy participants at clinical and supratherapeutic doses. Sixty-two participants were enrolled, stratified by sex, and randomized according to a crossover design among 4 treatment sequences: placebo, a single moxifloxacin 400-mg dose as positive c...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270009337943

    authors: Poordad F,Zeldin G,Harris SI,Ke J,Xu L,Mayers D,Zhou XJ

    更新日期:2009-12-01 00:00:00

  • Prolonged accumulation of diazepam in obesity.

    abstract::Six obese (mean weight 92 kg) and five normal (60 kg) subjects received 2 mg diazepam nightly for 30 nights. Determination of diazepam and desmethyldiazepam plasma concentrations during the dosing period and for a withdrawal period indicated that accumulation half-life for both diazepam (7.8 days in obese vs. 3.1 days...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1983.tb02750.x

    authors: Abernethy DR,Greenblatt DJ,Divoll M,Shader RI

    更新日期:1983-08-01 00:00:00

  • A Phase 1, Open-Label, Parallel-Group, Single-Dose Trial of the Pharmacokinetics and Safety of Cannabidiol (CBD) in Subjects With Mild to Severe Hepatic Impairment.

    abstract::The pharmacokinetics and safety of a single oral dose of 200-mg plant-derived pharmaceutical formulation of highly purified cannabidiol (CBD) in oral solution (Epidiolex in the United States; 100 mg/mL) were assessed in subjects with mild to severe hepatic impairment (n =  8 each for mild and moderate, n = 6 for sever...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,多中心研究

    doi:10.1002/jcph.1412

    authors: Taylor L,Crockett J,Tayo B,Morrison G

    更新日期:2019-08-01 00:00:00

  • The effect of rilpivirine on the pharmacokinetics of methadone in HIV-negative volunteers.

    abstract::Antiretrovirals may influence methadone exposure in HIV-1-infected patients receiving methadone for opiate addiction. Rilpivirine is a non-nucleoside reverse transcriptase inhibitor for treating HIV-1 infection. In this open-label trial (NCT00744770), 13 HIV-negative volunteers continued on their regular stable methad...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.222

    authors: Crauwels HM,van Heeswijk RP,Vandevoorde A,Buelens A,Stevens M,Hoetelmans RM

    更新日期:2014-02-01 00:00:00

  • Clinical pharmacokinetics of the CD19 receptor-directed tyrosine kinase inhibitor B43-Genistein in patients with B-lineage lymphoid malignancies.

    abstract::The authors examined the pharmacokinetics of the CD19 receptor-directed tyrosine kinase inhibitor B43-Genistein in 17 patients (4 children, 13 adults) with B-lineage lymphoid malignancies, including 12 patients with acute lymphoblastic leukemia (ALL) and 5 patients with non-Hodgkin's lymphoma (NHL). The immunoconjugat...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1177/00912709922012051

    authors: Chen CL,Levine A,Rao A,O'Neill K,Messinger Y,Myers DE,Goldman F,Hurvitz C,Casper JT,Uckun FM

    更新日期:1999-12-01 00:00:00

  • MAO-B and COMT Genetic Variations Associated With Levodopa Treatment Response in Patients With Parkinson's Disease.

    abstract::The most commonly used Parkinson's disease (PD) treatment is the replacement of dopamine by its levodopa precursor (l-dopa). Monoamine oxidase-B (MAO-B) and catechol-o-methyl transferase (COMT) are enzymes involved in the metabolism and regulation of dopamine availability. In our study we investigated the possible rel...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1096

    authors: Sampaio TF,Dos Santos EUD,de Lima GDC,Dos Anjos RSG,da Silva RC,Asano AGC,Asano NMJ,Crovella S,de Souza PRE

    更新日期:2018-07-01 00:00:00

  • Pharmacogenetic Analysis of OATP1B1, UGT1A1, and BCRP Variants in Relation to the Pharmacokinetics of Letermovir in Previously Conducted Clinical Studies.

    abstract::The cytomegalovirus (CMV) viral terminase inhibitor letermovir is indicated for prevention of CMV infection in CMV-seropositive allogeneic hematopoietic stem cell transplant recipients. In this analysis, functional variants in solute carrier organic anion transporter family member 1B1 (SLCO1B1), uridine diphosphate-gl...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1420

    authors: Kobie J,Guo Z,Cho CR,Menzel K,McCrea JB,Blanchard R,Shaw PM

    更新日期:2019-09-01 00:00:00

  • Multiple-dose phase I trials--normal volunteers or patients? One viewpoint.

    abstract::Traditionally, Phase I tolerance trials have been done with normal volunteers to establish single- and multiple-dose tolerance. We feel that the justification for doing multiple-dose tolerance studies in normals is open to question and that, in fact, more pertinent data can be generated by using the appropriate patien...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1981.tb01737.x

    authors: Weissman L

    更新日期:1981-10-01 00:00:00

  • Lack of effect of cimetidine on the pharmacokinetics of sustained-release bupropion.

    abstract::The objective of this study was to assess whether cimetidine affects the pharmacokinetics of sustained-release (SR) bupropion hydrochloride and the active metabolite, hydroxybupropion. This randomized, open-label, two-period crossover study was conducted in 24 healthy volunteers 18 to 45 years of age. ANOVA showed tha...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:

    authors: Kustra R,Corrigan B,Dunn J,Duncan B,Hsyu PH

    更新日期:1999-11-01 00:00:00

  • Entecavir pharmacokinetics, safety, and tolerability after multiple ascending doses in healthy subjects.

    abstract::A double-blind, placebo-controlled, multiple oral dose escalation study was conducted to investigate the pharmacokinetics, safety, and tolerability of entecavir in healthy subjects. Eight subjects were assigned to each of the 3 dose panels (0.1 mg, 0.5 mg, and 1 mg or matched placebo once daily for 14 days). Blood and...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270006293304

    authors: Yan JH,Bifano M,Olsen S,Smith RA,Zhang D,Grasela DM,LaCreta F

    更新日期:2006-11-01 00:00:00

  • Renin inhibition: a new approach to cardiovascular therapy.

    abstract::The renin-angiotensin system (RAS) functions as a primary regulator in the short-term and long-term control of blood pressure. Pharmacologic inhibition of the RAS with angiotensin-converting enzyme (ACE) inhibition is effective for treating systemic hypertension and congestive heart failure. As a more specific therapy...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1002/j.1552-4604.1994.tb04000.x

    authors: Frishman WH,Fozailoff A,Lin C,Dike C

    更新日期:1994-09-01 00:00:00

  • Evaluation of the Relationship of Glasdegib Exposure and Safety End Points in Patients With Refractory Solid Tumors and Hematologic Malignancies.

    abstract::Glasdegib is approved for treating acute myeloid leukemia in elderly patients at 100 mg once daily in combination with low-dose cytarabine. Exposure-efficacy analysis showed that the survival benefit of glasdegib was not glasdegib exposure-dependent. The relationship between glasdegib exposure and adverse event (AE) c...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1742

    authors: Ruiz-Garcia A,Shaik N,Lin S,Jamieson C,Heuser M,Chan G

    更新日期:2021-03-01 00:00:00

  • Pharmacokinetics of Nintedanib in Subjects With Hepatic Impairment.

    abstract::Nintedanib is an intracellular inhibitor of tyrosine kinases used in the treatment of non-small cell lung cancer and idiopathic pulmonary fibrosis (IPF). This phase 1 open-label study investigated the influence of mild and moderate hepatic impairment on the pharmacokinetics (PK), safety, and tolerability of nintedanib...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1025

    authors: Marzin K,Kretschmar G,Luedtke D,Kraemer S,Kuelzer R,Schlenker-Herceg R,Schmid U,Schnell D,Dallinger C

    更新日期:2018-03-01 00:00:00

  • Population pharmacokinetics of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in patients with type 2 diabetes.

    abstract::Data from five randomized, placebo-controlled, multiple oral dose studies of empagliflozin in patients with type 2 diabetes mellitus (T2DM; N = 974; 1-100 mg q.d.; ≤12 weeks) were used to develop a population pharmacokinetic (PK) model for empagliflozin. The model consisted of two-compartmental disposition, lagged fir...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1002/jcph.147

    authors: Riggs MM,Staab A,Seman L,MacGregor TR,Bergsma TT,Gastonguay MR,Macha S

    更新日期:2013-10-01 00:00:00

  • A review of potential cardiovascular uses of intravenous glucagon administration.

    abstract::Glucagon is a counter-regulatory hormone that is classically used to treat hypoglycemia. However, it can elicit the generation of cAMP within the myocardium to cause positive inotropic and chronotropic effects without the need for beta-1 adrenoceptor stimulation. Glucagon has been used extensively to treat beta-blocke...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:

    authors: White CM

    更新日期:1999-05-01 00:00:00

  • A Cross-Study Analysis Evaluating the Effects of Food on the Pharmacokinetics of Rivaroxaban in Clinical Studies.

    abstract::US prescribing guidelines recommend that 15- and 20-mg doses of rivaroxaban be administered with food for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) and for reduction in the risk of recurrence of DVT and PE. In addition, the US prescribing guidelines recommend these doses be administered w...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.958

    authors: Zhang L,Peters G,Haskell L,Patel P,Nandy P,Moore KT

    更新日期:2017-12-01 00:00:00

  • Single- and multiple-dose administration of caspofungin in patients with hepatic insufficiency: implications for safety and dosing recommendations.

    abstract::This report investigated safety and dosing recommendations of intravenous caspofungin in hepatic insufficiency. In the single-dose study, 8 patients each with mild and moderate hepatic insufficiency received 70 mg of caspofungin. In the multiple-dose study, 8 patients with mild hepatic insufficiency and 13 healthy mat...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/0091270007303764

    authors: Mistry GC,Migoya E,Deutsch PJ,Winchell G,Hesney M,Li S,Bi S,Dilzer S,Lasseter KC,Stone JA

    更新日期:2007-08-01 00:00:00

  • Dosing regimen of gentamicin during intermittent peritoneal dialysis.

    abstract::The peritoneal clearance of gentamicin was studied in 11 chronic uremic patients who undergoing intermittent peritoneal dialysis. Gentamicin was significantly removed by peritoneal dialysis with a clearance value of 9.75 +/- 3.78 ml/min. The serum half life was 14.08 +/- 3.57 hr, a value significantly less than that o...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1989.tb03302.x

    authors: Kaojarern S,Arkaravichien W,Indraprasit S,Pummangura C

    更新日期:1989-02-01 00:00:00

  • Multiple-dose plasma pharmacokinetic and safety study of LY450108 and LY451395 (AMPA receptor potentiators) and their concentration in cerebrospinal fluid in healthy human subjects.

    abstract::The objective of this study was to measure the steady-state cerebrospinal fluid (CSF) concentration of LY450108 and LY451395 (positive modulators of AMPA receptors) in healthy subjects after the administration of 1 mg and 5 mg. Secondary objectives included the evaluation of safety, pharmacokinetics, and steady-state ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/0091270006286899

    authors: Jhee SS,Chappell AS,Zarotsky V,Moran SV,Rosenthal M,Kim E,Chalon S,Toublanc N,Brandt J,Coutant DE,Ereshefsky L

    更新日期:2006-04-01 00:00:00

  • Armodafinil and modafinil in patients with excessive sleepiness associated with shift work disorder: a pharmacokinetic/pharmacodynamic model for predicting and comparing their concentration-effect relationships.

    abstract::Armodafinil, the longer lasting R-isomer of racemic modafinil, improves wakefulness in patients with excessive sleepiness associated with shift work disorder (SWD). Pharmacokinetic studies suggest that armodafinil achieves higher plasma concentrations than modafinil late in a dose interval following equal oral doses. ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270011417825

    authors: Darwish M,Bond M,Ezzet F

    更新日期:2012-09-01 00:00:00

  • Comparison of the administration of teneligliptin every day versus every other day in Japanese patients with type 2 diabetes: a randomized non-inferior test.

    abstract::The half life (t1/2 ) of teneligliptin is 24.2 hours. Accordingly, we hypothesized that the administration of teneligliptin every other day might improve glycemic control. In this study, we evaluated the effectiveness of the administration of teneligliptin every other day in Japanese patients with type 2 diabetes. Fif...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1002/jcph.385

    authors: Kamiko K,Aoki K,Kamiyama H,Taguri M,Shibata E,Ashiya Y,Minagawa F,Shinoda K,Nakajima S,Terauchi Y

    更新日期:2015-02-01 00:00:00

  • Estimation of Attainment of Steady-State Conditions for Compounds With a Long Half-Life.

    abstract::Half-life is a standard result reported with analysis of pharmacokinetic data. Different definitions such as noncompartmental half-life, terminal half-life, effective half-life, and context-sensitive half-life can yield substantially different estimates of the quantity "half-life." Time to attainment of steady-state c...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1701

    authors: Krause A,Lott D,Dingemanse J

    更新日期:2021-01-01 00:00:00

  • Pharmacokinetics, safety, and tolerability of paliperidone palmitate 3-month formulation in patients with schizophrenia: A phase-1, single-dose, randomized, open-label study.

    abstract::This multicenter, randomized, open-label, parallel-group, phase-1 study assessed the pharmacokinetics (PK), safety, and tolerability of the investigational intramuscular paliperidone palmitate 3-month (PP3M) formulation in patients with schizophrenia or schizoaffective disorder. A total of 328 patients (men or women, ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1002/jcph.597

    authors: Ravenstijn P,Remmerie B,Savitz A,Samtani MN,Nuamah I,Chang CT,De Meulder M,Hough D,Gopal S

    更新日期:2016-03-01 00:00:00