Dataset Information

A phase I pharmacokinetic and safety study of cabazitaxel in adult cancer patients with normal and impaired renal function.

ABSTRACT: Limited data are available on cabazitaxel pharmacokinetics in patients with renal impairment. This open-label, multicenter study assessed cabazitaxel in patients with advanced solid tumors and normal or impaired renal function.Cohorts A (normal renal function: creatinine clearance [CrCL] >80 mL/min/1.73 m2), B (moderate renal impairment: CrCL 30 to <50 mL/min/1.73 m2) and C (severe impairment: CrCL <30 mL/min/1.73 m2) received cabazitaxel 25 mg/m2 (A, B) or 20 mg/m2 (C, could be escalated to 25 mg/m2), once every 3 weeks. Pharmacokinetic parameters and cabazitaxel unbound fraction (F U) were assessed using linear regression and mixed models. Geometric mean (GM) and GM ratios (GMRs) were determined using mean CrCL intervals (moderate and severe renal impairment: 40 and 15 mL/min/1.73 m2) versus a control (90 mL/min/1.73 m2).Overall, 25 patients received cabazitaxel (median cycles: 3 [range 1-20]; Cohort A: 5 [2-13]; Cohort B: 3 [1-15]; and Cohort C: 5 [1-20]), of which 24 were eligible for pharmacokinetic analysis (eight in each cohort). For moderate and severe renal impairment versus normal renal function, GMR estimates were: clearance normalized to body surface area (CL/BSA) 0.95 (90% CI 0.80-1.13) and 0.89 (0.61-1.32); area under the curve normalized to dose (AUC/dose) 1.06 (0.88-1.27) and 1.14 (0.76-1.71); and F U 0.99 (0.94-1.04) and 0.97 (0.87-1.09), respectively. Estimated slopes of linear regression of log parameters versus log CrCL (renal impairment) were: CL/BSA 0.06 (-0.15 to 0.28); AUC/dose -0.07 (-0.30 to 0.16); and F U 0.02 (-0.05 to 0.08). Cabazitaxel safety profile was consistent with previous reports.Renal impairment had no clinically meaningful effect on cabazitaxel pharmacokinetics.

SUBMITTER: Azaro A

PROVIDER: S-EPMC5114328 | biostudies-other | 2016 Dec

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

A phase I pharmacokinetic and safety study of cabazitaxel in adult cancer patients with normal and impaired renal function.

Azaro Analía A Rodón Jordi J Machiels Jean-Pascal JP Rottey Sylvie S Damian Silvia S Baird Richard R Garcia-Corbacho Javier J Mathijssen Ron H J RHJ Clot Pierre-François PF Wack Claudine C Shen Liji L de Jonge Maja J A MJA

Cancer chemotherapy and pharmacology 20161027 6

<h4>Purpose</h4>Limited data are available on cabazitaxel pharmacokinetics in patients with renal impairment. This open-label, multicenter study assessed cabazitaxel in patients with advanced solid tumors and normal or impaired renal function.<h4>Methods</h4>Cohorts A (normal renal function: creatinine clearance [CrCL] >80 mL/min/1.73 m<sup>2</sup>), B (moderate renal impairment: CrCL 30 to <50 mL/min/1.73 m<sup>2</sup>) and C (severe impairment: CrCL <30 mL/min/1.73 m<sup>2</sup>) received caba ...[more]

PMID: 27796539

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Project description:Background: Ciprofol, a novel sedative-hypnotic drug, has been approved for its use in inducing and maintaining general anesthesia, as well as for providing sedation. Methods: In this phase I, single-center, parallel, controlled, open-label clinical trial, our objective was to analyze the pharmacokinetics (PK), pharmacodynamics (PD), and safety of ciprofol emulsion in 24 participants with mild and moderate renal impairment (n = 8 per group) and matched healthy participants (n = 8). An initial loading infusion of ciprofol was administered at 0.4 mg/kg for 1 min, followed by a maintenance infusion at a rate of 0.4 mg/kg/h for 30 min. We collected plasma and urine samples from the participants to assess the PK of ciprofol and its metabolite M4. The evaluation of PD involved using a modified observer's alertness/sedation scale (MOAA/S) in combination with bispectral index (BIS) monitoring. Safety assessments were conducted throughout the trial process. Results: The plasma concentration-time curve of ciprofol in participants with renal impairment was similar to that in participants with normal kidney function. The area under the curve (AUC) and maximum concentration (Cmax) of total and unbound ciprofol in plasma for participants with renal impairment were only slightly higher (0.7-1.2-fold) than those in participants with normal renal function. In contrast, for the metabolite M4, AUC values were 1.3- and 2.1-fold greater in participants with mild and moderate renal impairment, respectively, than in healthy controls. However, renal impairment had no significant impact on the PD parameters. The study found that ciprofol was well-tolerated, with all adverse events (AEs) reported being mild or moderate in severity. Conclusion: Based on these findings, we can conclude that no dosage adjustment of ciprofol is necessary for patients with mild-moderate renal impairment who receive the injection. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT04142970.

Project description:Vancomycin, a glycopeptide antibiotic for the treatment of grampositive infections, is mainly eliminated via glomerular filtration. Thus, its therapeutic effects are affected predominantly by renal function. The aim of this study was to develop a population pharmacokinetic model of vancomycin for Chinese adult patients and to investigate the influence of different renal function descriptors on the predictability of the model. A retrospective analysis was performed based on the blood concentrations of vancomycin in 218 Chinese adult patients. Among these patients, the data from 160 were used to establish the population pharmacokinetic model, and the data from the remaining 58 patients were used for external model validation. A simulation was employed to determine the appropriate initial vancomycin dosage regimens in adult Chinese patients for reaching the target steady-state trough concentrations of 10-15 mg/L and 15-20 mg/L. We developed a one-compartment model with first-order absorption to characterize the concentration-time profile of vancomycin. There was a positive correlation between the body clearance of vancomycin and renal function; both creatinine clearance (CLCr) and age were the covariates that influenced the PK of vancomycin, and the excretion of vancomycin decreased as renal function diminishing with age. The typical clearance (CL) value was 2.829 L/h for 75-year-old patients with CLCr values of 80 mL/min, and the rate constant of CL with the CLCr changing at 1 mL/min was 0.00842. The influence coefficient of age on CL was 0.08143. The external validation results revealed that the current different descriptors of renal function behaved similarly to the predicted performance of the models. In conclusion, the developed model is appropriate for Bayesian dose predictions of vancomycin concentrations in the population of Chinese adult patients. Furthermore, the simulation provides a reference for clinical optimized antibacterial therapy with vancomycin.

Dataset Information

A phase I pharmacokinetic and safety study of cabazitaxel in adult cancer patients with normal and impaired renal function.

Publications

A phase I pharmacokinetic and safety study of cabazitaxel in adult cancer patients with normal and impaired renal function.

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets