Stability of Bortezomib 1-mg/mL Solution in Plastic Syringe and Glass Vial

André, Pascal; Cisternino, Salvatore; Chiadmi, Fouad; Toledano, Audrey; Schlatter, Joël; Fain, Olivier; Fontan, Jean-Eudes

doi:10.1345/aph.1e620

Cited by 21 publications

(7 citation statements)

References 7 publications

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“…Figure 4 a, b, c and d show respectively the combination index values [ 32 ] for the combinations of CB, OX and CH1 with BORT in: A2780, A2780 cisR , A2780 ZD0473R and SKOV-3 cell lines. Combinations of CB with BORT were found to be synergistic in A2780, A2780 ZD0473R and SKOV-3 cell lines irrespective of the sequence of administration with the greatest cell kill resulting from the 0/2 h sequence.…”

Section: Resultsmentioning

confidence: 99%

Carboplatin and oxaliplatin in sequenced combination with bortezomib in ovarian tumour models

et al. 2013

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BackgroundOvarian cancer remains an on-going challenge mainly due to the development of drug resistance and also because the cancer is likely to have metastasized at the time of diagnosis. Currently, chemotherapy based on platinum drugs such as cisplatin is the primary treatment for the disease. Copper transporter 1 is involved in the transport of cisplatin into the cell, but is also down-regulated by the drug. Bortezomib, a proteasome inhibitor, has been reported to block this platinum-induced down-regulation of CTR1, so that in the presence of bortezomib, the cellular uptake of platinum drugs may be increased. Increased platinum accumulation may result in increased platinum − DNA binding so that the platinum drug in combination with bortezomib may produce enhanced cell kill.MethodsIn this study the efficacy of the sequential combinations of carboplatin, oxaliplatin and a trans-platinum compound coded as CH1 with BORT on the human ovarian A2780, A2780cisR, A2780ZD0473R and SKOV-3 cancer cell lines was evaluated. The levels of cellular platinum accumulation and platinum-DNA binding were determined following the treatment with these combinations. In order to investigate the effect of the combinations of the formation of ROS, the total and oxidized glutathione levels were also determined.ResultsPrevention of copper transporter 1 degradation by bortezomib is found to enhance the cellular accumulation of platinum, the level of Platinum − DNA binding and increases oxidative stress especially in the resistant cell lines.ConclusionsThe results suggest that the prevention of CTR1 degradation by bortezomib may be playing a major role in increasing the cellular uptake of platinum drugs and platinum-DNA binding level. Furthermore, the generation of oxidative stress appears to be a major contributor to the enhanced cell kill.

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Section: Resultsmentioning

confidence: 99%

Carboplatin and oxaliplatin in sequenced combination with bortezomib in ovarian tumour models

et al. 2013

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“…Solutions were sterilized by using filtration with a 0.45-μm syringe filter before use and shielded from light and stored at 4°C between uses. Fresh bortezomib solutions were prepared after 5 days in these storage conditions (18). …”

Section: Methodsmentioning

confidence: 99%

Pulsed High-Intensity Focused Ultrasound Enhances Apoptosis and Growth Inhibition of Squamous Cell Carcinoma Xenografts with Proteasome Inhibitor Bortezomib

Poff¹,

Allen²,

Traughber³

et al. 2008

Radiology

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Purpose: To investigate whether combining pulsed high-intensity focused ultrasound (HIFU) with the chemotherapeutic drug bortezomib could improve antitumor activity against murine squamous cell carcinoma (SCC) tumors. Materials and Methods: All experiments were conducted with animal care and use committee approval. Murine SCC cells were implanted subcutaneously in C3H mice. When tumors reached 100 mm3, mice were randomized to one of three groups for twice weekly intraperitoneal injections of 1.5 mg of bortezomib per kilogram of body weight, a proteasome inhibitor (n = 10); 1.0 mg/kg bortezomib (n = 11); or a control vehicle (n = 12). Within each group, half of the mice received pulsed HIFU exposure to their tumors immediately prior to each injection. The time for tumors to reach 650 mm3 was compared among groups. Additional tumors were stained with terminal deoxynucledotidyl transferase-mediated dUTP nick end labeling and CD31 to assess apoptotic index and blood vessel density, respectively. Results: Tumors in the control group, pulsed HIFU and control group, and 1.0 mg/kg of bortezomib alone group reached the size end point in 5.2 days ± 0.8 (standard deviation), 5.3 days ± 0.8, and 5.6 days ± 1.1, respectively. However, pulsed HIFU and 1.0 mg/kg bortezomib increased the time to end point to 9.8 days ± 2.9 (P < .02), not significantly different from the 8.8 days ± 2.1 in tumors treated with 1.5 mg/kg bortezomib alone (P > .05). Combination therapy was also associated with a significantly higher apoptotic index (P < .05). Conclusion: Treatment of tumors with pulsed HIFU lowered the threshold level for efficacy of bortezomib, resulting in significant tumor cytotoxicity and growth inhibition at lower dose levels.

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“…This study used the stability-indicating method of André and others, 5 which was validated in the authors' laboratory during the 2008 stability study of bortezomib. 3 A modified separation method was revalidated in the authors' laboratory before the current study began, according to accepted criteria.…”

Section: Chromatographic Analysismentioning

confidence: 99%

Stability of Bortezomib 2.5 mg/mL in Vials and Syringes Stored at 4°C and Room Temperature (23°C)

Walker

Charbonneau

Law

2014

CJHP

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Background: Solutions of bortezomib 1.0 mg/mL for IV administration are reportedly stable for up to 42 days. Recent publications have reported that the safety profile of bortezomib is better with subcutaneous administration than with IV administration.Objective: To evaluate the stability of higher-concentration bortezomib solutions for subcutaneous administration (i.e., 2.5 mg/mL in 0.9% sodium chloride [normal saline or NS]). Methods:On study day 0, twelve 3.5-mg vials of powdered bortezomib were each reconstituted with 1.4 mL of NS to prepare solutions with concentration 2.5 mg/mL. Half of the solutions were subsequently stored in the original vials and half were transferred to syringes. Three of each type of container were stored in the refrigerator (4°C) and the other 3 of each type were stored at room temperature (23°C). Concentration analysis and physical inspection were completed on study days 0, 1, 2, 8, 12, 14, 19, and 21. The concentration of bortezomib was determined by a validated liquid chromatographic method with ultraviolet detection. The expiry date was determined according to the time to achieve 90% of the initial concentration, based on the fastest degradation rate calculated from the 95% confidence interval of the observed degradation rate. Results:The analytical method separated degradation products from bortezomib such that the concentration was measured specifically and accurately (with absolute deviations from known concentration averaging 2.99%), with intraday and interday reproducibility averaging 1.51% and 2.51%, respectively. During the study period, all solutions were observed to retain at least 95.26% of the initial concentration in both types of containers at both temperatures.Conclusions: Bortezomib (3.5 mg in manufacturer's vial) reconstituted with 1.4 mL NS is physically and chemically stable for up to 21 days at 4°C or 23°C when stored in either the manufacturer's original glass vial or a syringe. Subcutaneous injection of bortezomib represents a change in practice, and there is a potential safety concern if a solution of the increased concentration used for subcutaneous administration (2.5 mg/mL) is inadvertently used to prepare a dose intended for IV administration. Therefore, it is recommended that sites switching to subcutaneous administration of bortezomib eliminate 1.0 mg/mL IV solutions altogether or institute substantial barriers to prevent IV administration of the higher concentration of bortezomib. RÉSUMÉContexte : Les solutions de bortézomib de 1,0 mg/mL pour administration intraveineuse sont jugées stables pour une période allant jusqu'à 42 jours. Des publications récentes indiquent que le profil d'innocuité du bortézomib est meilleur par administration sous-cutanée que par administration intraveineuse.Objectif : Évaluer la stabilité de solutions de bortézomib à concentration plus élevée pour l'administration sous-cutanée (c.-à-d., 2,5 mg/mL dans du chlorure de sodium à 0,9 % [solution physiologique salée ou SP])Méthodes : Au jour 0 de l'étude, on a reconsti...

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Stability of Bortezomib 1-mg/mL Solution in Plastic Syringe and Glass Vial

Abstract: BTZ stored refrigerated in vials or syringes and protected from light is chemically stable for 5 days after reconstitution.

Cited by 21 publications

References 7 publications

Carboplatin and oxaliplatin in sequenced combination with bortezomib in ovarian tumour models

Carboplatin and oxaliplatin in sequenced combination with bortezomib in ovarian tumour models

Pulsed High-Intensity Focused Ultrasound Enhances Apoptosis and Growth Inhibition of Squamous Cell Carcinoma Xenografts with Proteasome Inhibitor Bortezomib

Stability of Bortezomib 2.5 mg/mL in Vials and Syringes Stored at 4°C and Room Temperature (23°C)

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