Drug Exposure to Establish Pharmacokinetic–Response Relationships in Oncology

Solans, Belén P; Garrido, María J.; Trocóniz, Iñaki F.

doi:10.1007/s40262-019-00828-3

Cited by 6 publications

(3 citation statements)

References 130 publications

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“…Meanwhile, EtSevo-time AUC trend to have a continuous dose-dependent effect on EA risk. AUC is recommended as the primary measurement with drug absorption data by The Food and Drug Administration (FDA) ( 23 ), and is used in many research fields to assess certain levels of exposures, such as pharmacokinetics, chemistry, nutrition science, physics ( 24 , 25 ). In this study, we used GraphPad PRISM software to calculate EtSevo-time AUC, which is the definite integral of the concentration of EtSevo as a function of exposure time, and represented the total drug exposure.…”

Section: Discussionmentioning

confidence: 99%

Association of volatile anesthesia exposure and depth with emergence agitation and delirium in children: Prospective observational cohort study

Zhang

Zhang²,

Xu³

et al. 2023

Front. Pediatr.

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BackgroundSevoflurane anesthesia is widely used in pediatric ambulatory surgery. However, emergency agitation (EA) and emergency delirium (ED), as major complications following sevoflurane anesthesia in children, pose risks to surgery and prognosis. Identifying the high risk of EA/ED, especially anesthesia exposure and the depth of anesthesia, may allow preemptive treatment.MethodsA total of 137 patients were prospectively enrolled in this single-center observational cohort study to assess the incidence of EA or ED. Multivariable logistic regression analyses were used to test the association between volatile anesthesia exposure and depth with EA or ED. The Richmond Agitation and Sedation Scale (RASS), Pediatric Anesthesia Emergence Delirium Scale (PAED) and Face, Legs, Activity, Cry, and Consolability (FLACC) behavioural pain scale was used to assess the severity of EA or ED severity and pain. Bispectral index (BIS) to monitor the depth of anesthesia, as well as TimeLOW−BIS/TimeANES %, EtSevo (%) and EtSevo-time AUC were included in the multivariate logistic regression model as independent variables to analyze their association with EA or ED.ResultsThe overall prevalence of EA and ED was 73/137 (53.3%) and 75/137 (54.7%) respectively, where 48/137 (35.0%), 19/137 (13.9%), and 6/137 (4.4%) had mild, moderate, and severe EA. When the recovery period was lengthened, the prevalence of ED and extent of FLACC decreased and finally normalized within 30 min in recovered period. Multivariable logistic regression demonstrated that intraoperative agitation [2.84 (1.08, 7.47) p = 0.034], peak FLACC [2.56 (1.70, 3.85) p < 0.001] and adverse event (respiratory complications) [0.03 (0.00, 0.29) p = 0.003] were independently associated with higher odds of EA. Taking EtSevo-time AUC ≤ 2,000 as a reference, the incidence of EA were [15.84 (2.15, 116.98) p = 0.002] times and 16.59 (2.42, 113.83) p = 0.009] times for EtSevo-time AUC 2,500–3,000 and EtSevo-time AUC > 3,000, respectively. Peak FLACC [3.46 (2.13, 5.62) p < 0.001] and intraoperative agitation [5.61 (1.99, 15.86) p = 0.001] were independently associated with higher odds of developing ED. EtSevo (%), intraoperative BIS value and the percentage of the duration of anesthesia at different depths of anesthesia (BIS ≤ 40, BIS ≤ 30, BIS ≤ 20) were not associated with EA and ED.ConclusionsFor pediatrics undergoing ambulatory surgery where sevoflurane anesthesia was administered, EA was associated with surgical time, peak FLACC, respiratory complications, and “EtSevo-time AUC” with a dose-response relationship; ED was associated with peak FLACC and intraoperative agitation.

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Section: Discussionmentioning

confidence: 99%

Association of volatile anesthesia exposure and depth with emergence agitation and delirium in children: Prospective observational cohort study

Zhang

Zhang²,

Xu³

et al. 2023

Front. Pediatr.

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“…On the one hand, initially planned dose reductions based on, i.e., older age or comorbidity, or empirically capped BSA at 2.0 m 2 for chemotherapy dosing in patients with severe obesity, are individual patient evaluations introduced in attempt to limit excess toxicity or overdosing and improve treatment tolerability. On the other hand, these decisions may result in unnecessary reduced chemotherapy delivery in some older and obese patients [28,29] due to pharmacokinetics with variability in drug metabolism between patients receiving the same chemotherapy regimens [30].…”

Section: Discussionmentioning

confidence: 99%

Patient-Related Characteristics Associated with Treatment Modifications and Suboptimal Relative Dose Intensity of Neoadjuvant Chemotherapy in Patients with Breast Cancer—A Retrospective Study

Kjeldsted

Gehl

Sørensen

et al. 2023

Cancers

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Background: Reduced relative dose intensity (RDI) of neoadjuvant chemotherapy (NACT) in patients with breast cancer may compromise treatment outcome and survival. We examined patient-related characteristics associated with treatment modifications and suboptimal RDI and tumour response in patients with breast cancer. Methods: In this observational study, electronic medical records were reviewed retrospectively for female patients with breast cancer scheduled for NACT at a university hospital in Denmark between 2017 and 2019. The RDI (ratio of delivered dose intensity in relation to standard dose intensity) was calculated. Multivariate logistic regression analyses examined associations of sociodemographics, general health and clinical cancer characteristics with dose reductions, dose delays, discontinuation of NACT and suboptimal RDI < 85%. Results: Among 122 included patients, 43%, 42% and 28% experienced dose reductions, dose delays ≥3 days and discontinuation, respectively. A total of 25% received an RDI < 85%. Comorbidity, taking long-term medications and being overweight were statistically significantly associated with treatment modifications, while age ≥ 65 years and comorbidity were associated with RDI < 85%. Around one third of all patients had radiologic (36%) or pathologic (35%) complete tumour response, with no statistically significant differences by RDI < or ≥85% irrespective of breast cancer subtype. Conclusions: While most patients had RDI ≥85%, still one out of four patients received an RDI < 85%. Further investigations of possible supportive care initiatives to improve patients’ treatment tolerability are needed, particularly among subgroups of older age or with comorbidity.

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“…Pharmacometrics is defined as "the science of developing and applying mathematical and statistical methods to (a) characterize, understand, and predict a drug's pharmacokinetic and pharmacodynamic behaviour; (b) quantify uncertainty of information about that behaviour; and (c) rationalize data-driven decision making in the drug development process and pharmacotherapy" (13). Pharmacometric modelling and simulation techniques can help understand the relationship between drug exposure and the subsequent effects, which is particularly important for determining the appropriate dose setting for each patient (14). Almost all anticancer agents have narrow therapeutic windows, and there are large inter-and intra-individual variabilities in drug exposure.…”

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confidence: 99%

Application of Pharmacometrics of 5-Fluorouracil to Personalized Medicine: A Tool for Predicting Pharmacokinetic–Pharmacodynamic/Toxicodynamic Responses

Kobuchi

Ito

2020

Anticancer Res

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Drug Exposure to Establish Pharmacokinetic–Response Relationships in Oncology

Cited by 6 publications

References 130 publications

Association of volatile anesthesia exposure and depth with emergence agitation and delirium in children: Prospective observational cohort study

Association of volatile anesthesia exposure and depth with emergence agitation and delirium in children: Prospective observational cohort study

Patient-Related Characteristics Associated with Treatment Modifications and Suboptimal Relative Dose Intensity of Neoadjuvant Chemotherapy in Patients with Breast Cancer—A Retrospective Study

Application of Pharmacometrics of 5-Fluorouracil to Personalized Medicine: A Tool for Predicting Pharmacokinetic–Pharmacodynamic/Toxicodynamic Responses

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