Randomized Crossover Pharmacokinetic Study of Solvent-Based Paclitaxel and nab -Paclitaxel
Open accessAbstract
Purpose: Abraxane (ABI-007) is a 130-nm albumin-bound (nab) particle formulation of paclitaxel, devoid of any additional excipients. We hypothesized that this change in formulation alters the systemic disposition of paclitaxel compared with conventional solvent-based formulations (sb-paclitaxel; Taxol), and leads to improved tolerability of the drug. Patients and Methods: Patients with malignant solid tumors were randomized to receive the recommended single-agent dose of nab-paclitaxel (260 mg/m2 as a 30-minute infusion) or sb-paclitaxel (175 mg/m2 as a 3-hour infusion). After cycle 1, patients crossed over to the alternate treatment. Pharmacokinetic studies were carried out for the first cycle of sb-paclitaxel and the first two cycles of nab-paclitaxel. Results: Seventeen patients were treated, with 14 receiving at least one cycle each of nab-paclitaxel and sb-paclitaxel. No change in nab-paclitaxel pharmacokinetics was found between the first and second cycles (P = 0.95), suggesting limited intrasubject variability. Total drug exposure was comparable between the two formulations (P = 0.55) despite the dose difference. However, exposure to unbound paclitaxel was significantly higher after nab-paclitaxel administration, due to the increased free fraction (0.063 ± 0.021 versus 0.024 ± 0.009; P < 0.001). Conclusion: This study shows that paclitaxel disposition is subject to considerable variability depending on the formulation used. Because systemic exposure to unbound paclitaxel is likely a driving force behind tumoral uptake, these findings explain, at least in part, previous observations that the administration of nab-paclitaxel is associated with augmented antitumor efficacy compared with solvent-based paclitaxel.
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Taxane concentrations in the plasma of patients with cancer during chemotherapy reach between 0.1 and 1 μM.
“A compound concentration of at least 5 µM was needed to induce a substantial effect (Fig. 1a,e), whereas taxane concentrations in the plasma of patients with cancer during chemotherapy reach concentrations of between 0.1 and 1 µM (refs. 47,48).”
From Taxane-induced conformational changes in the microtubule lattice activate GEF-H1-dependent RhoA signalling (2026) · cites this paper as [47]
The Results (Unbound paclitaxel pharmacokinetics; page unavailable) report an unbound peak of 121.79 ng/mL for solvent-based paclitaxel, approximately 0.14 μM, within the claimed range. But the unbound peak for nab-paclitaxel is approximately 1.5 μM, and the reported total-plasma peaks are higher still. The paper therefore supports a concentration within 0.1–1 μM for one regimen’s unbound drug, not that the range generally describes plasma taxane concentrations during chemotherapy. (LLM, conf=0.87)
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Research works printed but not linked: 17
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- Authors
- Gardner, E. R., Dahut, W. L., Scripture, C. D., Jones, J., Aragon-Ching, J. B., Desai, N., Hawkins, M. J., Sparreboom, A., & Figg, W. D.
- Affiliations
- National Cancer Institute (US)
- 2Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland; and
- Abraxis (United States) (US)
- Corresponding author
- Figg, William D.
- Venue
- Clinical Cancer Research
- Published
- 2008-07-01
- Volume
- 14
- Issue
- 13
- Pages
- 4200-4205
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC2661025
- OpenAlex
- W2060597541
- Cited by
- 226
- References
- 0
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 9 · 2023: 12 · 2022: 13 · 2021: 15 · 2020: 16 · 2019: 15 · 2018: 13 · 2017: 16 · 2016: 16 · 2015: 16 · 2014: 21 · 2013: 13 · 2012: 5
- FWCI
- 4.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01co12400-79-0-22, NIH0011335962)
- National Cancer Institute (Z01BC010548, N01-CO-012400, Z01SC010098, Z01SC006537)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- nab-paclitaxel, paclitaxel, pharmacokinetics, drug formulation, unbound drug fraction, drug exposure, solid tumors, antitumor efficacy
- MeSH terms
- Adult, Aged, Albumins, Antineoplastic Agents, Phytogenic, Breast Neoplasms, Carcinoma, Fallopian Tube Neoplasms, Female, Humans, Male, Middle Aged, Ovarian Neoplasms, Prostatic Neoplasms, Solvents, Paclitaxel, Cross-Over Studies
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