scholarly journals Population Pharmacokinetics of Palbociclib in aReal-World Situation

2021 ◽  
Vol 14 (3) ◽  
pp. 181
Author(s):  
Bernard Royer ◽  
Courèche Kaderbhaï ◽  
Jean-David Fumet ◽  
Audrey Hennequin ◽  
Isabelle Desmoulins ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Real World ◽  
Kinase Inhibitor ◽  
Metastatic Breast ◽  
Compartment Model ◽  
Cancer Center ◽  
First Order ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Apparent Clearance ◽  
Lag Times

Palbociclib is an oral cyclin-dependent kinase inhibitor that is used in combination with aromatase inhibitors in the treatment of postmenopausal women with metastatic breast cancer. Its metabolism profile is associated with an important interpatient variability. We performed a population pharmacokinetics study of palbociclib in women routinely followed in a cancer center. One hundred and fifty-one samples were analyzed. The sampling times after administration ranged from 0.9 to 75 h and the samples were taken between 1 and 21 days after the beginning of the palbociclib cycle. Palbociclib was determined using a validated mass spectrometry method. The best model that described the concentrations was a one-compartment model with first-order absorption and an absorption lag time. Interindividual variability could only be estimated on the clearance and the first-order absorption. Creatinine clearance was found to be a significant covariate for the apparent clearance. No significant covariates could be observed with the first-order absorption. First-order absorption and absorption lag times were difficult to assess because of the constraints linked to the real-world setting due to the small number of samples used during the absorption process. However, palbociclib apparent clearance was satisfactorily estimated. Population pharmacokinetics (POP PK) with palbociclib could help to optimize dosing.

scholarly journals Population Pharmacokinetics of Nevirapine, Zidovudine, and Didanosine in Human Immunodeficiency Virus-Infected Patients

1999 ◽  
Vol 43 (1) ◽  
pp. 121-128 ◽  
Author(s):  
Xiao-Jian Zhou ◽  
Lewis B. Sheiner ◽  
Richard T. D’Aquila ◽  
Michael D. Hughes ◽  
Martin S. Hirsch ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Body Weight ◽  
Population Pharmacokinetics ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Zero Order ◽  
Triple Combination ◽  
Entire Study ◽  
First Order ◽  
Immunodeficiency Virus

ABSTRACT The population pharmacokinetics of nevirapine (NVP), zidovudine (ZDV), and didanosine (ddI) were evaluated in a total of 175 patients infected with human immunodeficiency virus randomized to receive either a double combination of ZDV plus ddI or a triple combination of NVP plus ZDV plus ddI as a substudy of the AIDS Clinical Trials Group Protocol 241. Levels (approximating 3.5 determinations/patient) of the three drugs in plasma were measured during 44 of a total 48 weeks of study treatment, and a set of potential covariates was available for nonlinear mixed-effect modeling analysis. A one-compartment model with zero-order input and first-order elimination was fitted to the NVP data. Individual oral clearance (CL) and volume of distribution (V) averaged 0.0533 liters/h/kg of body weight and 1.17 liters/kg, respectively. Gender was the only covariate which significantly correlated with the CL of NVP. ZDV and ddI data were described by a two-compartment model with zero-order input and first-order elimination. Individual mean oral CL,V SS (volume of distribution at steady state), and V of ZDV were 1.84 liters/h/kg and 6.68 and 2.67 liters/kg, respectively, with body weight and age as correlates of CL and body weight as a correlate of V SS. The average individual oral CL, V SS, andV of ddI were 1.64 liters/h/kg and 3.56 and 2.74 liters/kg, respectively, with body weight as a significant correlate of both CL and V SS. The relative bioavailability (F) of ZDV and ddI in the triple combination compared to that in the double combination was also evaluated. No significant effects of the combination regimens on the F of ddI were detected (F TRIPLE = 1.05 andF DOUBLE = 1 by definition), but theF of ZDV was markedly reduced by the triple combination, being only 67.7% of that of the double combination. Large (>50%) intraindividual variability was associated with both ZDV and ddI pharmacokinetics. Individual cumulative area under the plasma drug level-time curve of the three drugs was calculated for the entire study period as a measure of drug exposure based on the individual data and the final-model estimates of structural and statistical parameters.

scholarly journals Retrospective Analysis of Treatment Patterns and Effectiveness of Palbociclib and Subsequent Regimens in Metastatic Breast Cancer

2019 ◽  
Vol 17 (2) ◽  
pp. 141-147 ◽  
Author(s):  
Jing Xi ◽  
Aabha Oza ◽  
Shana Thomas ◽  
Foluso Ademuyiwa ◽  
Katherine Weilbaecher ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Hormone Therapy ◽  
Real World ◽  
Metastatic Breast ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Rank Test ◽  
Cancer Center ◽  
Targeted Agents

Background: Cyclin-dependent kinase (CDK) 4/6 inhibitors are now the standard of care for hormone receptor–positive (HR+), HER2-negative (HER–) metastatic breast cancer (MBC). However, guidelines are lacking regarding their optimal sequencing with other available agents. This study examines physician practice patterns and treatment outcomes of palbociclib and subsequent therapies in a real-world setting. Methods: A retrospective chart review was conducted for consecutive patients with MBC who received palbociclib between February 2015 and August 2017 at the Alvin J. Siteman Cancer Center. Kaplan-Meier method was used to generate time-to-event curves and estimate median progression-free survival (mPFS). Log-rank test was used to compare differences. Results: A total of 200 patients, with a median age of 59.4 years and a follow-up of 19.5 months, were included. Palbociclib was most frequently combined with letrozole (73.5%), followed by fulvestrant (25%), anastrozole (1%), and tamoxifen (0.5%). Most patients received palbociclib in the endocrine-resistant setting (n=42, n=50, and n=108 in the first-, second-, and subsequent-line settings, respectively), and the fraction of patients receiving palbociclib as first- or second-line therapy increased in recent months (P=.0428). mPFS was 20.7, 12.8, and 4.0 months with palbociclib administered in the first-, second-, and subsequent-line settings, respectively (P<.0001). Incidences of grade 3/4 neutropenia (41.5%) and dose reductions (29%) were comparable to reports in the literature. Among patients whose disease progressed on palbociclib (n=104), the most frequent next-line treatment was capecitabine (n=21), followed by eribulin (n=16), nab-paclitaxel (n=15), and exemestane + everolimus (n=12). mPFS with hormone therapy alone or in combination with targeted agents (n=32) after first-, second-, and subsequent-line palbociclib was 17.0, 9.3, and 4.2 months, respectively (P=.04). mPFS with chemotherapy (n=70) was not reached, 4.7, and 4.1 months after first-, second-, and subsequent-line palbociclib, respectively (P=.56). Conclusions: Palbociclib is effective for HR+/HER2– MBC in real-world practice. Hormone therapy alone or in combination with targeted agents remains an effective option after palbociclib progression.

scholarly journals The Efficacy of Pyrotinib as a Third- or Higher-Line Treatment in HER2-Positive Metastatic Breast Cancer Patients Exposed to Lapatinib Compared to Lapatinib-Naive Patients: A Real-World Study

2021 ◽  
Vol 12 ◽  
Author(s):  
D. J Ouyang ◽  
Q. T Chen ◽  
M. Anwar ◽  
N. Xie ◽  
Q. C. Ouyang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Real World ◽  
Kinase Inhibitor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Original Cohort

Background: Pyrotinib is a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor. Evidence of the efficacy of pyrotinib-based treatments for HER2-positive metastatic breast cancer (MBC) in patients exposed to lapatinib is limited.Methods: Ninety-four patients who received pyrotinib as a third- or higher-line treatment for HER2-positive MBC were included in this retrospective study. The primary and secondary endpoints were overall survival (OS) and progression‐free survival (PFS). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analysis were implemented to balance important patient characteristics between groups.Results: Thirty (31.9%) patients were pretreated with lapatinib and subsequently received pyrotinib as an anti-HER2 treatment, and 64 (68.1%) patients did not receive this treatment. The OS and PFS indicated a beneficial trend in lapatinib-naive group compared to lapatinib-treated group in either the original cohort (PFS: 9.02 vs 6.36 months, p = 0.05; OS: 20.73 vs 14.35 months, p = 0.08) or the PSM (PFS: 9.02 vs 6.08 months, p = 0.07; OS: 19.07 vs 18.00 months, p = 0.61) or IPTW (PFS: 9.90 vs 6.17 months, p = 0.05; OS: 19.53 vs 15.10 months, p = 0.08) cohorts. Subgroup analyses demonstrated lapatinib treatment-related differences in PFS in the premenopausal subgroup and the no prior trastuzumab treatment subgroup, but no significant differences were observed in OS.Conclusion: Pyrotinib-based therapy demonstrated promising effects in HER2-positive MBC patients in a real-world study, especially in lapatinib-naive patients, and also some activity in lapatinib-treated patients.

scholarly journals Pyrotinib Plus Vinorelbine Versus Lapatinib Plus Capecitabine in Patients With Previously Treated HER2-Positive Metastatic Breast Cancer: A Multicenter, Retrospective Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Yizhao Xie ◽  
Yi Li ◽  
Luo Ting ◽  
Die Sang ◽  
Peng Yuan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Real World ◽  
Kinase Inhibitor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Trastuzumab Resistance ◽  
Her2 Positive ◽  
Oral Vinorelbine

BackgroundPyrotinib is a newly-developed irreversible pan-ErbB (erythroblastic leukemia viral oncogene homolog) receptor oral tyrosine kinase inhibitor (TKI) with promising efficacy in the human epidermal growth factor receptor-2 (HER2) positive breast cancer. The phase III PHOEBE study proved that pyrotinib plus capecitabine exceeded lapatinib plus capecitabine (LX) in PFS (p &lt; 0.001). Oral vinorelbine is commonly used in combination with anti-HER2 treatment. However, no evidence was reported in terms of the real-world pattern, safety, and efficacy of pyrotinib plus vinorelbine (NP) compared with LX.MethodsMedical records were retrospectively evaluated for all HER2-positive metastatic breast cancer (MBC) patients who experienced progression on prior trastuzumab-containing regimens (advanced setting) and taxane (any setting) and received NP or LX therapy from 2015 to 2021 in five institutions.ResultsA total of 224 patients were enrolled and evaluated, of which 132 (58.9%) patients received LX and 92 (41.1%) patients received NP. The median progression-free survival (mPFS) of NP group was significantly longer than that in LX group (8.3 vs 5.0 months, HR = 0.47 95% CI 0.34–0.65, p &lt; 0.001). The advantage of NP over LX was seen both in patients with trastuzumab resistance (p &lt; 0.001) and refractoriness (p = 0.004). The NP group had more diarrhea cases (23.9%) compared to the LX group (8.3%). Discontinuation rates in the two groups were similar.ConclusionsThis trial revealed the clinical practice of NP and LX treatment among HER2+ MBC patients pretreated with trastuzumab in China. More patients received LX than NP in real-world while the efficacy of NP exceeded LX in terms of PFS regardless of resistant status of trastuzumab. Although the NP group had more diarrhea cases, toxicities in both groups were acceptable.

scholarly journals Population Pharmacokinetics of Cis-, Trans-, and Total Cefprozil in Healthy Male Koreans

Pharmaceutics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 531 ◽  
Author(s):  
Ji-Hun Jang ◽  
Seung-Hyun Jeong ◽  
Hea-Young Cho ◽  
Yong-Bok Lee
Keyword(s):  
Population Pharmacokinetics ◽  
Demographic Data ◽  
Compartment Model ◽  
Healthy Male ◽  
First Order ◽  
Dosing Algorithm ◽  
Subject Variability ◽  
Cephalosporin Antibiotics ◽  
Parameter Values ◽  
First Time

Cefprozil, one of cephalosporin antibiotics, has been used extensively in clinics. However, pharmacokinetic (PK) information on cefprozil is still very limited. There have been no reports of population pharmacokinetics (PPKs). A PPK model for cefprozil will be a great advantage for clinical use. Thus, the aim of this study was to develop a PPK model for cefprozil for healthy male Koreans. Clinical PK and demographic data of healthy Korean males receiving cefprozil at a dose of 1000 mg were analyzed using Phoenix® NLME™. A one-compartment model with first-order absorption with lag-time was constructed as a base model. The model was extended to include covariates that influenced between-subject variability. Creatinine clearance significantly influenced systemic clearance of cefprozil. The final PPK model for cis-, trans-, and total cefprozil was established and validated. PPK parameter values of cis- and total cefprozil were similar to each other, but different from those of trans-isomer. Herein, we describe the establishment of accurate PPK models of cis-, trans-, and total cefprozil for healthy male Koreans for the first time. It may be useful as a dosing algorithm for the general population. These results might also contribute to the development of stereoisomeric cefprozil.

Sign in / Sign up

Export Citation Format

Share Document