Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pharmacokinetics of alectinib and its metabolite M4 in a patient with advanced lung adenocarcinoma undergoing hemodialysis: A case report.

ABSTRACT: This study presents the first detailed pharmacokinetic data of alectinib and its metabolite M4 in a patient with anaplastic lymphoma kinase (ALK)-rearranged lung adenocarcinoma undergoing hemodialysis. When the patient was administered a daily 300 mg bid dose of alectinib, the maximal observed plasma concentration (C_max ) of alectinib and M4 were 638 and 82 ng/ml, respectively, at steady-state (day 9). These pharmacokinetic data were similar to those previously reported in patients with normal organ function. The trough plasma concentration (C_trough ) of alectinib and M4 on the hemodialysis day were 562 and 66 ng/ml, respectively, identical to those on post-hemodialysis day. He remains well and in partial remission 12 months after his diagnosis. We believe that alectinib is feasible and effective for patients with ALK-rearranged non-small cell lung cancer undergoing hemodialysis.

SUBMITTER: Park JE

PROVIDER: S-EPMC9013650 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Pharmacokinetics of alectinib and its metabolite M4 in a patient with advanced lung adenocarcinoma undergoing hemodialysis: A case report.

Park Ji Eun JE Yoon Young-Ran YR Kim Chang Ho CH Lee Jaehee J

Thoracic cancer 20220222 8

This study presents the first detailed pharmacokinetic data of alectinib and its metabolite M4 in a patient with anaplastic lymphoma kinase (ALK)-rearranged lung adenocarcinoma undergoing hemodialysis. When the patient was administered a daily 300 mg bid dose of alectinib, the maximal observed plasma concentration (Cmax ) of alectinib and M4 were 638 and 82 ng/ml, respectively, at steady-state (day 9). These pharmacokinetic data were similar to those previously reported in patients wi ...[more]

PMID: 35191596

Similar Datasets

Pharmacokinetics of Temozolomide in a Patient With Glioblastoma Undergoing Hemodialysis: A Short Communication.

Project description:BackgroundTemozolomide (TMZ) is an alkylating agent used to treat glioblastoma. However, the pharmacokinetics of TMZ to establish a treatment strategy for patients undergoing hemodialysis (HD) remain unclear. In this case report, we evaluated the pharmacokinetics and HD removal rate of TMZ in a patient with glioblastoma undergoing HD to determine optimal dosing of TMZ.MethodsA 78-year-old man with glioblastoma who underwent HD 3 times a week was treated with TMZ concomitant with radiotherapy. One dose of TMZ was prescribed at 75 mg/m2 on the day before HD and another dose of 37.5 mg/m2 on the day before non-HD. Peak and trough concentrations (1 hour and 12 hours after dosing, respectively) were evaluated before HD and on non-HD days. HD removal rate of TMZ was calculated based on the predialyzer and postdialyzer plasma concentrations. Furthermore, the TMZ plasma concentrations were measured using liquid chromatography-tandem mass spectrometry.ResultsThe mean plasma peak and trough concentrations ± SD after 75 mg/m2 TMZ were 2917 ± 914 and 108 ± 17.6 ng/mL, respectively. Those after 37.5 mg/m2 TMZ dosage were 1305 ± 650 and 53.8 ± 11.8 ng/mL, respectively. The mean HD TMZ removal rate was 84.9 ± 1.9%.ConclusionsTMZ was tolerable in patients undergoing HD. Based on the data from a single individual pharmacokinetic perspective, the pharmacokinetics of TMZ in this patient undergoing HD were comparable with those observed in patients with normal renal function. In addition, it may be reasonable to administer TMZ after HD because of the high HD removal rate.

| S-EPMC10635330 | biostudies-literature

Recurrent "Flexispira rappini" bacteremia in an adult patient undergoing hemodialysis: case report.

Project description:A blood culture from a 65-year-old febrile man undergoing hemodialysis revealed, 5 days after inoculation, an unusual gram-negative fusiform rod with darting motility. During another episode of fever 21 days later, this Campylobacter-like organism was again recovered from three blood cultures and subcultured under an H2-enriched microaerobic atmosphere. The organism was catalase negative and oxidase positive and hydrolyzed urea rapidly. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of whole-cell proteins was indistinguishable from that of "Flexispira rappini" LMG 8738 described by Archer et al. in 1988 (J. R. Archer, S. Romero, A. E. Ritchier, M. E. Hamacher, B. M. Steiner, J. H. Bryner, and R. F. Schell, J. Clin. Microbiol. 26:101-105, 1988). The analysis of the 16S ribosomal DNA sequence revealed a similarity of 99.3% between the two strains. The patient recovered completely after a 4-week course of meropenem therapy. This is the first reported case of a recurrent "F. rappini" bacteremia in an adult patient, which confirms that this organism may be an invasive pathogen in immunocompromised patients, like other newly described Helicobacter species.

| S-EPMC84762 | biostudies-literature

Pharmacokinetic analysis of gefitinib in a patient with advanced non-small cell lung cancer undergoing hemodialysis.

Project description:Patients undergoing hemodialysis (HD) are frequently elderly with poor performance status and usually cannot withstand chemotherapy because of its toxicities. We report a case of an elderly woman with chronic renal failure undergoing HD who was diagnosed with advanced non-small cell lung cancer and treated with orally administered gefitinib. We analyzed the pharmacokinetic data of gefitinib in this patient and found that that gefitinib was safe under these conditions.

| S-EPMC4773293 | biostudies-other

Novel PPFIA1-ALK, ALK-C2orf91(intergenic) double-fusion responded well to alectinib in an advanced lung adenocarcinoma patient: a case report.

Project description:Non-small cell lung cancers (NSCLCs) with anaplastic lymphoma kinase (ALK)-rearrangement have favorable responses to ALK inhibitors. However, ALK fusion mutations harbored approximately 90 distinct fusion partners. Patients with different ALK fusions might respond distinctly to different-generation ALK inhibitors. In this case report, we identified a novel non-reciprocal ALK fusion, ALK-C2orf91(intergenic) (A19: intergenic) and PPFIA1-ALK (P2:A20), by next-generation DNA sequencing in an advanced lung adenocarcinoma patient. After 2 months of alectinib, the targeted lung lesion regressed significantly, and evaluation of therapeutic efficiency indicated partial response. To date, the patient had achieved 12 months of progression-free survival from alectinib treatment. Our study extended the spectrum of ALK fusion partners in ALK-positive NSCLC, and we reported a new ALK fusion, PPFIA1-ALK and ALK-C2orf91(intergenic), and its sensitivity to alectinib firstly in lung cancer. We believe that this case report has an important clinical reference.

| S-EPMC10497211 | biostudies-literature

Perioperative alectinib in a patient with locally advanced anaplastic lymphoma kinase positive non-small cell lung cancer (NSCLC): a case report

Project description:We reported a case of locally advanced anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patient who received neoadjuvant alectinib therapy. Enhanced computed tomography (CT) scan was performed after the first cycle of alectinib therapy to evaluate the efficacy of neoadjuvant alectinib. Surprisingly, the tumor shrunk 42.2% after one cycle treatment. Partial remission (PR) was achieved without any side effects, although the tumor stage didn’t degrade. Then right upper lobectomy and mediastinal lymph node dissection by video assistant thoracoscopic surgery (VATS) were successfully performed after multi-disciplinary team meeting with the department of respiratory, thoracic surgery, radiotherapy (RT), pathology and radiology. Pathologic evaluation about tumor was assessed by hematoxylin and eosin staining. However, the residual viable tumor cells were 15%, which indicated that major pathologic response (MPR) was not achieved. Next, continually adjuvant alectinib and RT were given because mediastinal station 4R lymphadenectomy excluded with serious tissue adhesion and MPR status was not met. In this case, we presented neoadjuvant alectinib therapy was feasible and well tolerated in locally advanced ALK positive NSCLC, inspiring clinical studies to further assess its clinical implication in treating patients with locally advanced ALK-positive NSCLC. And we also discussed the necessary time of neoadjuvant and adjuvant alectinib in advanced ALK-positive NSCLC.

| S-EPMC8799071 | biostudies-literature

Case Report: sintilimab-induced Stevens-Johnson Syndrome in a patient with advanced lung adenocarcinoma.

Project description:Immune checkpoint inhibitors (ICIs) have been widely applicated in clinical therapy in recent years. Skin-related adverse reaction is one of the most common adverse events for ICIs. Stevens-Johnson syndrome (SJS) is one of the serious cutaneous reactions threatening the life. Here, we reported a case of 76-year-old male patient with poorly differentiated metastatic lung adenocarcinoma, after 9 weeks exposure of sintilimab (3 doses) combined with paclitaxel liposome after concurrent chemotherapy/radiotherapy, experienced Stevens-Johnson syndrome involving limbs, trunk, lip and the oral mucosa. Biopsy of the skin tissue showed infiltration of CD4 and CD8 positive T lymphocytes. We also found PD-L1 expression in the glands and the basal layer of the skin. This finding is distinct from the previously reported expression of PD-L1 on the surface of epidermal keratinocytes in patients with SJS due to immunotherapy.

| S-EPMC10540079 | biostudies-literature

Immune myocarditis related to sintilimab treatment in a patient with advanced lung adenocarcinoma: A case report

Project description:Immune checkpoint inhibitors (ICI) have improved clinical outcomes of patients with advanced lung cancer, but may lead to fatal cardiac injury. We describe a 66-year-old man with advanced lung adenocarcinoma who presented with chest pain and dyspnea 3 weeks after the first dose of sintilimab. The initial electrocardiogram (ECG) demonstrated ST-elevation in leads V5-V9, and a high-sensitivity troponin level was significantly elevated. However, coronary angiography did not reveal any significant stenosis. The patient was successfully treated with methylprednisolone and immunoglobulin. Cardiac MRI was carried out before discharge and late gadolinium enhancement (LGE) was found to be in the mid layer of the septal segment and the subepicardial layer of the inferolateral wall. Due to the high fatality, ICI-related myocarditis requires close surveillance, prompt management and long-term follow-up.

| S-EPMC9582520 | biostudies-literature

Effect of Hepatic Impairment on the Pharmacokinetics of Alectinib.

Project description:Alectinib is approved and recommended as the preferred first-line treatment for patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer. The effect of hepatic impairment on the pharmacokinetics (PK) of alectinib was assessed with physiologically based PK modeling prospectively and in a clinical study. An open-label study (NCT02621047) investigated a single 300-mg dose of alectinib in moderate (n = 8) and severe (n = 8) hepatic impairment (Child-Pugh B/C), and healthy subjects (n = 12) matched for age, sex, and body weight. Physiologically based PK modeling was conducted prospectively to inform the clinical study design and support the use of a lower dose and extended PK sampling in the study. PK parameters were calculated for alectinib, its major similarly active metabolite, M4, and the combined exposure of alectinib and M4. Unbound concentrations were assessed at 6 and 12 hours postdose. Administration of alectinib to subjects with hepatic impairment increased the area under the plasma concentration-time curve from time 0 to infinity of the combined exposure of alectinib and M4 to 136% (90% confidence interval [CI], 94.7-196) and 176% (90%CI 98.4-315), for moderate and severe hepatic impairment, respectively, relative to matched healthy subjects. Unbound concentrations for alectinib and M4 did not appear substantially different between hepatic-impaired and healthy subjects. Moderate hepatic impairment had only a modest, not clinically significant effect on alectinib exposure, while the higher exposure observed in severe hepatic impairment supports a dose adjustment in this population.

| S-EPMC6282775 | biostudies-literature

Daptomycin Pharmacokinetics in Adolescents Undergoing Hemodialysis and Peritoneal Dialysis: A Case Series With Pharmacokinetic Modeling.

Project description:BackgroundChildren who undergo hemodialysis (HD) and peritoneal dialysis are at increased risk of infection. Daptomcyin is used to treat resistant infections; however, the pharmacokinetics of daptomycin in pediatric and adolescent dialysis patients remain unknown.MethodsWe report the safety and pharmacokinetics of a single intravenous 5 mg/kg dose of daptomycin for 6 individuals age 12 to 17 years old who underwent HD or continuous cycling peritoneal dialysis (CCPD). Daptomycin concentrations from all samples were determined by high-performance liquid chromatography. A non-compartmental analysis was performed to compare the pharmacokinetic parameters among HD and CCPD patients. A population pharmacokinetic model was developed to describe the concentration-time profiles of daptomycin in plasma, urine, and dialysis effluent. Monte Carlo simulations were performed to assess the pharmacodynamic outcomes.ResultsAll subjects tolerated the single dose of daptomycin. During HD, significant drug removal was observed, compared with CCPD (26% vs 5% of total dose). A low daptomycin renal clearance (<12% of total clearance) with moderate variability (40.5%) was observed among subjects with residual renal function. An anuric and obese subject who received CCPD treatment appeared to have >80% higher daptomycin area under the plasma concentration-time curve than the other CCPD subjects. Dosing regimens that achieved predefined pharmacodynamic targets were reported.ConclusionsDaptomycin clearance was faster in 12- to 17-year-old patients receiving HD than CCPD. Administration of daptomycin immediately after HD reduces drug loss. The CCPD treatment, anuria, and obesity may increase the risk for drug accumulation. Our pharmacokinetic model can be further used to optimize dosing regimens of daptomycin in this population.

| S-EPMC7887886 | biostudies-literature

Case report: BRAF A598-T599insV mutation as a potential resistance mechanism to alectinib in ALK-rearranged lung adenocarcinoma.

Project description:Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have improved the prognosis of advanced-stage non-small cell lung cancer (NSCLC) with ALK rearrangement, but resistance mechanisms limit their efficacy. We describe the case of a 63-year-old man with a stage cIVA ALK-rearranged lung adenocarcinoma who developed a BRAF A598-T599insV mutation as a potential resistance mechanism to alectinib, a second-generation ALK TKI. He was treated with an association of BRAF and MEK inhibitors but death occurred two months after treatment initiation in a context of tumor progression and toxicity. Based on this first report of BRAF A598-T599insV mutation occurring in lung cancer, we discuss resistance mechanisms to ALK TKIs, implications of BRAF mutation in NSCLC, and BRAF A598-T599insV mutation in other cancers.

| S-EPMC9677532 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data