Population pharmacokinetics of doxorubicin: A systematic review

Methaneethorn, Janthima; Tengcharoen, Kanokkan; Leelakanok, Nattawut; AlEjielat, Rowan

doi:10.1111/ajco.13776

Cited by 5 publications

(2 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, a significant number of publications showed its applicability in the treatment of different forms of skin cancer [ 27 , 28 , 29 , 30 ]. After systemic application, doxorubicin is distributed non-specifically and therefore may cause undesirable toxic effects in healthy tissues [ 31 , 32 ]. Its lack of specificity, the need of high doses and low concentration at the cancer site are prerequisite for toxicity issues such as myelosuppression, cardiotoxicity and alopecia [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

Composite Hydrogel with Oleic Acid-Grafted Mesoporous Silica Nanoparticles for Enhanced Topical Delivery of Doxorubicin

Slavkova,

Dimitrova,

Voycheva

et al. 2024

Gels

View full text Add to dashboard Cite

Mesoporous silica nanoparticles (MSNs) are inorganic nanocarriers presenting versatile properties and the possibility to deliver drug molecules via different routes of application. Their modification with lipids could diminish the burst release profile for water-soluble molecules. In the case of oleic acid (OA) as a lipid component, an improvement in skin penetration can be expected. Therefore, in the present study, aminopropyl-functionalized MSNs were modified with oleic acid through carbodiimide chemistry and were subsequently incorporated into a semisolid hydrogel for dermal delivery. Doxorubicin served as a model drug. The FT-IR and XRD analysis as well as the ninhydrin reaction showed the successful preparation of the proposed nanocarrier with a uniform particle size (352–449 nm) and negative zeta potential. Transmission electron microscopy was applied to evaluate any possible changes in morphology. High encapsulation efficiency (97.6 ± 1.8%) was achieved together with a sustained release profile over 48 h. The composite hydrogels containing the OA-modified nanoparticles were characterized by excellent physiochemical properties (pH of 6.9; occlusion factor of 53.9; spreadability of factor 2.87 and viscosity of 1486 Pa·s) for dermal application. The in vitro permeation study showed 2.35 fold improvement compared with the hydrogel containing free drug. In vitro cell studies showed that loading in OA-modified nanoparticles significantly improved doxorubicin’s cytotoxic effects toward epidermoid carcinoma cells (A431). All of the results suggest that the prepared composite hydrogel has potential for dermal delivery of doxorubicin in the treatment of skin cancer.

show abstract

Section: Introductionmentioning

confidence: 99%

Composite Hydrogel with Oleic Acid-Grafted Mesoporous Silica Nanoparticles for Enhanced Topical Delivery of Doxorubicin

Slavkova,

Dimitrova,

Voycheva

et al. 2024

Gels

View full text Add to dashboard Cite

show abstract

“…This failure is dose-dependent, when the dose exceeds 450–550 mg/m 2 and there is no effective prevention or treatment ( 6 , 7 ). Moreover, the apparent volume of distribution (V d ) is quite large, ranging from 20-30 L/kg, suggesting an extensive tissue uptake ( 8 ). These shortcomings limit the clinical application of anthracyclines.…”

Section: Introductionmentioning

confidence: 99%

A multicenter randomized trials to compare the bioequivalence and safety of a generic doxorubicin hydrochloride liposome injection with Caelyx ® in advanced breast cancer

Wang

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

PurposeTo compare the pharmacokinetic (PK) bioequivalence (BE) and safety of a generic pegylated liposomal doxorubicin (PLD) formulation with the reference product Caelyx®.MethodsA multicenter, single-dose, open-label, randomized, two-way crossover study was conducted in patients with breast cancer. For each period, the patients were administered with the test or the reference PLD intravenously at a dose of 50 mg/m2. Cmax, AUC0−t and AUC0−∞ for free, and encapsulated doxorubicin (doxorubicin) and partial AUC (AUC0−48h, AUC48h−t) for encapsulated doxorubicin were evaluated in 17 blood samples taken predose, and increasing time intervals over the following 14 days in each period. A washout period of 28-35 days was observed before crossing over.Results48 patients were enrolled and randomised, of which 44 were included and analysed in bioequivalence set (BES). The 90% confidence intervals (CIs) of the geometric mean ratio (GMR) of Cmax, AUC0−t and AUC0−∞ for free doxorubicin and encapsulated doxorubicin all fall within the bioequivalent range of 80% to 125%. The 90% CIs of GMR of partial AUC (AUC0−48h, AUC48h−t) for encapsulated doxorubicin also fall within the bioequivalent range. 48 patients were all included in the safety set (SS). The incidence of treatment-emergent adverse events (TEAEs) related to T and R was 95.8% (46/48) and 97.8% (45/46) respectively. The highest incidence of TEAEs was various laboratory abnormalities. 2 patients withdrew due to T-drug-related AEs. Only one patient experienced serious adverse events and no death occurred in this study. There were no significant differences between the safety profiles of the generic formulation and Caelyx®.ConclusionsBioequivalence between the test and the reference products was established for free and encapsulated doxorubicin.Clinical trial registrationhttp://www.chinadrugtrials.org.cn, identifier [CTR20210375].

show abstract

Population pharmacokinetics of TLD-1, a novel liposomal doxorubicin, in a phase I trial

Mc Laughlin,

Hess,

Michelet

et al. 2024

Cancer Chemother Pharmacol

View full text Add to dashboard Cite

Study objectives TLD-1 is a novel pegylated liposomal doxorubicin (PLD) formulation aiming to optimise the PLD efficacy-toxicity ratio. We aimed to characterise TLD-1’s population pharmacokinetics using non-compartmental analysis and nonlinear mixed-effects modelling. Methods The PK of TLD-1 was analysed by performing a non-compartmental analysis of longitudinal doxorubicin plasma concentration measurements obtained from a clinical trial in 30 patients with advanced solid tumours across a 4.5-fold dose range. Furthermore, a joint parent-metabolite PK model of doxorubicinentrapped, doxorubicinfree, and metabolite doxorubicinol was developed. Interindividual and interoccasion variability around the typical PK parameters and potential covariates to explain parts of this variability were explored. Results Medians $$\pm$$ ± standard deviations of dose-normalised doxorubicinentrapped+free Cmax and AUC0−∞ were 0.342 $$\pm$$ ± 0.134 mg/L and 40.1 $$\pm$$ ± 18.9 mg·h/L, respectively. The median half-life (95 h) was 23.5 h longer than the half-life of currently marketed PLD. The novel joint parent-metabolite model comprised a one-compartment model with linear release (doxorubicinentrapped), a two-compartment model with linear elimination (doxorubicinfree), and a one-compartment model with linear elimination for doxorubicinol. Body surface area on the volumes of distribution for free doxorubicin was the only significant covariate. Conclusion The population PK of TLD-1, including its release and main metabolite, were successfully characterised using non-compartmental and compartmental analyses. Based on its long half-life, TLD-1 presents a promising candidate for further clinical development. The PK characteristics form the basis to investigate TLD-1 exposure-response (i.e., clinical efficacy) and exposure-toxicity relationships in the future. Once such relationships have been established, the developed population PK model can be further used in model-informed precision dosing strategies. Clinical trial registration ClinicalTrials.gov–NCT03387917–January 2, 2018

show abstract

Population pharmacokinetics of doxorubicin: A systematic review

Cited by 5 publications

References 37 publications

Composite Hydrogel with Oleic Acid-Grafted Mesoporous Silica Nanoparticles for Enhanced Topical Delivery of Doxorubicin

Composite Hydrogel with Oleic Acid-Grafted Mesoporous Silica Nanoparticles for Enhanced Topical Delivery of Doxorubicin

A multicenter randomized trials to compare the bioequivalence and safety of a generic doxorubicin hydrochloride liposome injection with Caelyx ® in advanced breast cancer

Population pharmacokinetics of TLD-1, a novel liposomal doxorubicin, in a phase I trial

Contact Info

Product

Resources

About