Dataset Information

A survey of renal impairment pharmacokinetic studies for new oncology drug approvals in the USA from 2010 to early 2015: a focus on development strategies and future directions.

ABSTRACT: The US Food and Drug Administration (FDA) issued a guidance document in 2010 on pharmacokinetic (PK) studies in renal impairment (RI) on the basis of observations that substances such as uremic toxins might result in altered drug metabolism and excretion. No specific recommendations for oncology drugs were included. We surveyed the publicly available FDA review documents of 29 small molecule oncology drugs approved between 2010 and the first quarter of 2015. The objectives were as follows: (i) summarize the impact of RI on PK at the time of the initial new drug application; (ii) identify limitations of the guidance; and (iii) outline an integrated approach to study the impact of RI on these drugs. Our survey indicates that the current FDA guidance does not appear to provide clear strategic or decision pathways for RI studies in terms of small molecule oncology drugs. The FDA review documents indicate an individualized approach to the review because of the complex pharmacologic nature of these drugs and patient populations. Overall, the strategy for carrying out a RI study during clinical development or as a postmarketing study requires integration with the totality of data, including mass balance, absolute bioavailability, drug-drug interaction, hepatic dysfunction, population PK, exposure-response analysis, the therapeutic window for best guidance, and determination of the optimal doses for special oncology populations.

SUBMITTER: Xiao JJ

PROVIDER: S-EPMC5515635 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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A survey of renal impairment pharmacokinetic studies for new oncology drug approvals in the USA from 2010 to early 2015: a focus on development strategies and future directions.

Xiao Jim J JJ Chen Jiyun S JS Lum Bert L BL Graham Richard A RA

Anti-cancer drugs 20170801 7

The US Food and Drug Administration (FDA) issued a guidance document in 2010 on pharmacokinetic (PK) studies in renal impairment (RI) on the basis of observations that substances such as uremic toxins might result in altered drug metabolism and excretion. No specific recommendations for oncology drugs were included. We surveyed the publicly available FDA review documents of 29 small molecule oncology drugs approved between 2010 and the first quarter of 2015. The objectives were as follows: (i) s ...[more]

PMID: 28542036

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Project description:As increased growth and development put pressure on freshwater systems in Arctic environments, there is a need to maintain a meaningful and feasible framework for monitoring water quality. A useful tool for monitoring the ecological health of aquatic systems is by means of the analysis and inferences made from benthic invertebrates in a biomonitoring approach. Biomonitoring of rivers and streams within the Arctic has been under-represented in research efforts. Here, we investigate an approach for monitoring biological impairment in Arctic streams from anthropogenic land use at two streams with different exposure to urban development in Iqaluit, Nunavut, Arctic Canada. Sites upstream of development, at midpoint locations, and at the mouth of each waterbody were sampled during 6 campaigns (2008, 2009, 2014, 2015, 2018, and 2019) to address spatial and temporal variability of the macroinvertebrate community. The influence of taxonomic resolution scaling was also examined in order to understand the sensitivity of macroinvertebrates as indicators in Arctic aquatic systems. We demonstrate that standard biological metrics were effective in indicating biological impairment downstream of sources of point-source pollutants. A mixed-design ANOVA for repeated measures also found strong interannual variability; however, we did not detect intra-annual variation from seasonal factors. When examining metrics at the highest taxonomic resolution possible, the sensitivity of metrics increased. Likewise, when trait-based metrics (α functional diversity) were applied to indicators identified at high taxonomic resolution, a significant difference was found between reference and impacted sites. Our results show that even though Arctic systems have lower diversity and constrained life-history characteristics compared to temperate ecosystems, biomonitoring is not only possible, but also equally effective in detecting trends from anthropogenic activities. Thus, biomonitoring approaches in Arctic environments are likely a useful means for providing rapid and cost-effective means of assessing future environmental impact.

Dataset Information

A survey of renal impairment pharmacokinetic studies for new oncology drug approvals in the USA from 2010 to early 2015: a focus on development strategies and future directions.

Publications

A survey of renal impairment pharmacokinetic studies for new oncology drug approvals in the USA from 2010 to early 2015: a focus on development strategies and future directions.

Similar Datasets

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