Validation of an HPLC-UV method for sorafenib determination in human plasma and application to cancer patients in routine clinical practice

Blanchet, Benoı̂t; Billemont, Bertrand; Cramard, Julie; Benichou, Anne Sophie; Chhun, Stéphanie; Harcouët, Laura; Ropert, Stanislas; Dauphin, A.; Goldwasser, François; Tod, Michel

doi:10.1016/j.jpba.2009.02.008

Cited by 111 publications

(82 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…sorafenib level. This observation was similar to those in other reports (Blanchet et al 2009;Boudou-Rouquette et al 2012) and suggests that sorafenib-related adverse effects are correlated with serum concentration of the drug. Therefore, we ascertained the association between dosage reduction/withdrawal of sorafenib and the AUC of sorafenib or sorafenib N-oxide during days 1-7 in 25 patients with HCC.…”

Section: Discussionsupporting

confidence: 92%

“…Recently, Blanchet et al (2009) reported that the plasma concentration of sorafenib in patients with adverse effects (grade > 3) is 1.5-fold higher than in patients with no adverse effects. Boudou-Rouquette et al (2012) also reported that the AUC of sorafenib is associated with the highest risk of developing any type of grade ≥ 3 toxicity.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Monitoring Serum Levels of Sorafenib and Its <i>N</i>-Oxide Is Essential for Long-Term Sorafenib Treatment of Patients with Hepatocellular Carcinoma

Shimada

Okawa

Kondo

et al. 2015

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Sorafenib, an oral multi-kinase inhibitor, is the final therapy prior to palliative care for advanced hepatocellular carcinoma (HCC). However, due to its adverse effects, 20% of patients must discontinue sorafenib within 1 month after first administration. To identify ways to predict the adverse effects and administer the drug for longer periods, we explored the relationship between the duration of sorafenib treatment and the pharmacokinetics of sorafenib and its major metabolite, sorafenib N-oxide. Twenty-five subjects enrolled in the study were divided into two groups: patients with dosage reduced or withdrawn due to adverse effects (n = 8), and patients with dosage maintained for 1 month after initial administration (n = 17). We evaluated early sorafenib accumulation as the area under the curve of sorafenib and sorafenib N-oxide concentrations during days 1-7 (AUC sorafenib and AUC N-oxide , respectively). Inter-group comparison revealed that AUC N-oxide and AUC ratio (AUC N-oxide /AUC sorafenib ) were significantly higher in the dosage reduction/withdrawal group (P = 0.031 and P = 0.0022, respectively). Receiver operating characteristic analysis indicated that AUC N-oxide and AUC ratio were reliable predictors of adverse effects. When patients were classified by cut-off points (AUC N-oxide : 2.0 μg•day/mL, AUC ratio: 0.13), progression-free survival was significantly longer in patients with AUC N-oxide ≤ 2.0 μg•day/mL (P = 0.0048, log-rank test). In conclusion, we recommend to simultaneously monitor serum levels of sorafenib and its N-oxide during the early stage after the first administration, which enables us to provide safe and long-term therapy for each HCC patient with sorafenib.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Monitoring Serum Levels of Sorafenib and Its <i>N</i>-Oxide Is Essential for Long-Term Sorafenib Treatment of Patients with Hepatocellular Carcinoma

Shimada

Okawa

Kondo

et al. 2015

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

show abstract

“…In the human pharmacokinetic studies, the mean peak plasma level of sorafenib was approximately 13.5 mmol/L (6.2 mg/mL) with a mean half-life of 35 hours in patients with advanced solid tumors (30). These data suggest that the in vitro concentration of sorafenib (2.5 mmol/L, used in our experiments) is much lower than those obtained in the plasma after therapeutic treatment, and it has considerable potential of ideal chemosensitizer that should not be toxic itself.…”

Section: Discussionmentioning

confidence: 99%

New Use for an Old Drug: Inhibiting ABCG2 with Sorafenib

Wei

Zhao

et al. 2012

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Human ABCG2, a member of the ATP-binding cassette transporter superfamily, represents a promising target for sensitizing MDR in cancer chemotherapy. Although lots of ABCG2 inhibitors were identified, none of them has been tested clinically, maybe because of several problems such as toxicity or safety and pharmacokinetic uncertainty of compounds with novel chemical structures. One efficient solution is to rediscover new uses for existing drugs with known pharmacokinetics and safety profiles. Here, we found the new use for sorafenib, which has a dual-mode action by inducing ABCG2 degradation in lysosome in addition to inhibiting its function. Previously, we reported some novel dual-acting ABCG2 inhibitors that showed closer similarity to degradation-induced mechanism of action. On the basis of these ABCG2 inhibitors with diverse chemical structures, we developed a pharmacophore model for identifying the critical pharmacophore features necessary for dual-acting ABCG2 inhibitors. Sorafenib forms impressive alignment with the pharmacophore hypothesis, supporting the argument that sorafenib is a potential ABCG2 inhibitor. This is the first article that sorafenib may be a good candidate for chemosensitizing agent targeting ABCG2-mediated MDR. This study may facilitate the rediscovery of new functions of structurally diverse old drugs and provide a more effective and safe way of sensitizing MDR in cancer chemotherapy.

show abstract

“…A patient series found that sorafenib C min was higher in patients who experienced Grade 3 AEs ( n = 8) than those who did not ( n = 14), 7.7 ± 3.6 mg/L vs. 4.4 ± 2.4 mg/L ( P = 0.0083) 68. Sorafenib steady‐state concentrations were found to be higher in patients with Grade ≥2 hand‐foot syndrome and hypertension than in those not experiencing these AEs ( P = 0.0045 and 0.0453, respectively).…”

Section: Practical Recommendations For Tdm Of Kis In Oncologymentioning

confidence: 98%

Practical Recommendations for Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology

Verheijen

Schellens

et al. 2017

Clin Pharma and Therapeutics

228

287

View full text Add to dashboard Cite

Despite the fact that pharmacokinetic exposure of kinase inhibitors (KIs) is highly variable and clear relationships exist between exposure and treatment outcomes, fixed dosing is still standard practice. This review aims to summarize the available clinical pharmacokinetic and pharmacodynamic data into practical guidelines for individualized dosing of KIs through therapeutic drug monitoring (TDM). Additionally, we provide an overview of prospective TDM trials and discuss the future steps needed for further implementation of TDM of KIs.

show abstract

Validation of an HPLC-UV method for sorafenib determination in human plasma and application to cancer patients in routine clinical practice

Cited by 111 publications

References 17 publications

Monitoring Serum Levels of Sorafenib and Its <i>N</i>-Oxide Is Essential for Long-Term Sorafenib Treatment of Patients with Hepatocellular Carcinoma

Monitoring Serum Levels of Sorafenib and Its <i>N</i>-Oxide Is Essential for Long-Term Sorafenib Treatment of Patients with Hepatocellular Carcinoma

New Use for an Old Drug: Inhibiting ABCG2 with Sorafenib

Practical Recommendations for Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology

Contact Info

Product

Resources

About