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Clinical Pharmacokinetics of Paclitaxel Monotherapy: An Updated Literature Review.

ABSTRACT: Paclitaxel is an anticancer agent efficacious in the treatment of ovarian, breast, and lung cancer. Due to a strong link between the pharmacokinetics and therapeutic efficacy of paclitaxel, we reviewed the literature on paclitaxel pharmacokinetics. Systematic data mining was performed to extract the maximum concentration (C _max), clearance (CL), and time of paclitaxel plasma concentration above 0.05 µmol/L (T > 0.05 µmol/L) following monotherapy of both the widely used cremophor-diluted paclitaxel and nanoparticle albumin-bound (nab-)paclitaxel. We identified a total of 53 studies yielding 121 aggregated pharmacokinetic profiles for paclitaxel monotherapy and extracted reported mean and median estimates of pharmacokinetic parameters. Paclitaxel has been studied formally at doses of 15-825 mg/m² and infused over 0.5-96 h; included studies examined both weekly and every 3-weeks dosing cycles. The most widely used dose of cremophor-diluted paclitaxel, 175 mg/m² given as a 3-h infusion, leads to an interstudy median C _max of 5.1 µmol/L [interquartile range (IQR) 4.5-5.7], CL of 12.0 L/h/m² (IQR 10.9-12.9), and T > 0.05 µmol/L of 23.8 h (IQR 21.5-26.8). Importantly, the significant interindividual variation widely reported in the literature is not reflected in these interstudy estimates of pharmacokinetic parameters. Cremophor-diluted paclitaxel pharmacokinetics are non-linear following short (<6 h) but not long (>24 h) infusions. A similar pattern of non-linearity was observed for nab-paclitaxel, although the number of studies was limited. The pharmacokinetics of paclitaxel monotherapy have been widely studied at numerous dose levels of the Cremophor EL^® formulation, but are less well-characterized for the newer nab-paclitaxel formulation. In conclusion, paclitaxel pharmacokinetics are non-linear for short infusion times but not for longer infusions. Whether a similar conclusion can be drawn for nab-paclitaxel formulations requires further study.

SUBMITTER: Stage TB

PROVIDER: S-EPMC8572663 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundA previous review on compassion in healthcare (1988-2014) identified several empirical studies and their limitations. Given the large influx and the disparate nature of the topic within the healthcare literature over the past 5 years, the objective of this study was to provide an update to our original scoping review to provide a current and comprehensive map of the literature to guide future research and to identify gaps and limitations that remain unaddressed.MethodsEight electronic databases along with the grey literature were searched to identify empirical studies published between 2015 and 2020. Of focus were studies that aimed to explore compassion within the clinical setting, or interventions or educational programs for improving compassion, sampling clinicians and/or patient populations. Following title and abstract review, two reviewers independently screened full-text articles, and performed data extraction. Utilizing a narrative synthesis approach, data were mapped onto the categories, themes, and subthemes that were identified in the original review. Newly identified categories were discussed among the team until consensus was achieved.ResultsOf the 14,166 number of records identified, 5263 remained after removal of duplicates, and 50 articles were included in the final review. Studies were predominantly conducted in the UK and were qualitative in design. In contrast to the original review, a larger number of studies sampled solely patients (n = 12), and the remainder focused on clinicians (n = 27) or a mix of clinicians and other (e.g. patients and/or family members) (n = 11). Forty-six studies explored perspectives on the nature of compassion or compassionate behaviours, traversing six themes: nature of compassion, development of compassion, interpersonal factors related to compassion, action and practical compassion, barriers and enablers of compassion, and outcomes of compassion. Four studies reported on the category of educational or clinical interventions, a notable decrease compared to the 10 studies identified in the original review.ConclusionsSince the original scoping review on compassion in healthcare, while a greater number of studies incorporated patient perspectives, clinical or educational interventions appeared to be limited. More efficacious and evidence-based interventions or training programs tailored towards improving compassion for patients in healthcare is required.

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Clinical Pharmacokinetics of Paclitaxel Monotherapy: An Updated Literature Review.

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