Pharmacokinetics of enzalutamide, an anti-prostate cancer drug, in rats

  title={Pharmacokinetics of enzalutamide, an anti-prostate cancer drug, in rats},
  author={Tae-Heon Kim and Jong-Woo Jeong and Ji-Hye Song and Kyeong-Ryoon Lee and Sunjoo Ahn and Sung-Hoon Ahn and Sungsub Kim and Tae-Sung Koo},
  journal={Archives of Pharmacal Research},
Abstract We characterized the pharmacokinetics of enzalutamide, a novel anti-prostate cancer drug, in rats after intravenous and oral administration in the dose range 0.5–5 mg/kg. Tissue distribution, liver microsomal stability, and plasma protein binding were also examined. After intravenous injection, systemic clearance, volumes of distribution at steady state (Vss), and half-life (T½) remained unaltered as a function of dose, with values in the ranges of 80.4–86.3 mL/h/kg, 1020–1250 mL/kg… 

Pharmacokinetics of tafamidis, a transthyretin amyloidosis drug, in rats

Tafamidis undergoes minimal first-pass metabolism, distributes mostly in the liver and plasma, and appears to be eliminated primarily via biliary excretion.

Synthesis and Evaluation of F-Enzalutamide, a New Radioligand for PET Imaging of Androgen Receptors: A Comparison with 16b-F-Fluoro-5a-Dihydrotestosterone

F-enzalutamide shows higher tumor uptake and better metabolic stability than FFDHT and thus seems to have more favorable properties for imaging of AR with PET, but further evaluation in other oncologic animal models and patients is warranted to confirm these results.

Synthesis and Evaluation of 18F-Enzalutamide, a New Radioligand for PET Imaging of Androgen Receptors: A Comparison with 16β-18F-Fluoro-5α-Dihydrotestosterone

18F-enzalutamide shows higher tumor uptake and better metabolic stability than 18F-FDHT and thus seems to have more favorable properties for imaging of AR with PET, but further evaluation in other oncologic animal models and patients is warranted to confirm these results.

Intravenous delivery of enzalutamide based on high drug loading multifunctional graphene oxide nanoparticles for castration-resistant prostate cancer therapy

A multifunctional nanocarrier constructed here could accomplish controlled Enz release and serve as an intravenous therapy platform for CRPC and exhibited an enhanced cancer-targeting ability and alleviated the side effects of Enz in vivo.

A Validated Stability Indicating RP-HPLC Method Development for Anticancer Drug Enzalutamide in Bulk and Pharmaceuticals

A reproducible stability-indicating Reverse Phase-HPLC technique for the quantification of Enzalutamide in in pharmaceuticals was developed and validated. Chromatography was done on Inertsil ODS-C18

Novel Treatment Strategy Using Second-Generation Androgen Receptor Inhibitors for Non-Metastatic Castration-Resistant Prostate Cancer

APA, ENZA, and DARO should be considered the new standard drugs for treating nmCRPC with substantial improvements in metastasis-free survival (MFS) and OS in phase III randomized clinical trials.

Dose considerations for anti‐cancer drugs in metastatic prostate cancer

Drug‐specific issues that may be associated with unexpected or unrecognized variations in drug systemic exposure despite the use of protocol doses are reviewed.

Chromatographic Methods for Determination of Drugs Used in Prostate Cancer in Biological and Pharmacological Samples

  • C. Saka
  • Biology, Chemistry
    Critical reviews in analytical chemistry
  • 2019
This review article contains a summary of analyzes performed by chromatographic methods used for the determination of abiraterone acetate, bicalutamide, cabazitaxel, docetaxel and enzalutamide used in prostate cancer applications in biological and pharmacological samples.

Quality by Design–Applied Liquid Chromatography-Tandem Mass Spectrometry Determination of Enzalutamide Anti-Prostate Cancer Therapy Drug in Spiked Plasma Samples

The Quality by Design–finalised conditions for a method that uses liquid chromatography-tandem mass spectrometry for the determination of concentration of enzalutamide (ENZ), an atypical anticancer drug, in a drug formulation and in spiked plasma samples are presented.



Pharmacokinetics, brain distribution, and plasma protein binding of the antiepileptic drug lacosamide in rats

After intravenous injection, terminal half-life, systemic clearance, and steady state volumes of distribution remained unaltered as a function of dose with values in the range 3.01–3.53 h, 221–241 mL/h/kg and 702–732 mL/kg, respectively.

Increased survival with enzalutamide in prostate cancer after chemotherapy.

Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy, and was shown with respect to all secondary end points.

Quantitative determination of enzalutamide, an anti-prostate cancer drug, in rat plasma using liquid chromatography-tandem mass spectrometry, and its application to a pharmacokinetic study.

This analytical method could be successfully applied to the pharmacokinetic study of enzalutamide in rats and demonstrated a linear standard curve over a concentration range of 0.001-1 µg/mL and an intra- and inter-assay precision of 2.7 and 5.1%.

Enzalutamide as a second generation antiandrogen for treatment of advanced prostate cancer

Enzalutamide is a novel second generation antiandrogen that has been demonstrated to significantly improve survival in men with metastatic CRPC in several clinical trials and its limitations for treatment of CRPC are discussed.

A controlled trial of leuprolide with and without flutamide in prostatic carcinoma.

Treatment with le uprolide and flutamide is superior to treatment with leuprolide alone in patients with advanced prostate cancer, and Symptomatic improvement was greatest during the first 12 weeks of the combined androgen blockade.

Development of a Second-Generation Antiandrogen for Treatment of Advanced Prostate Cancer

The diarylthiohydantoins RD162 and MDV3100 are characterized, two compounds optimized from a screen for nonsteroidal antiandrogens that retain activity in the setting of increased androgen receptor expression that appear to be promising candidates for treatment of advanced prostate cancer.

Hepatic clearance of drugs. I. Theoretical considerations of a “well-stirred” model and a “parallel tube” model. Influence of hepatic blood flow, plasma and blood cell binding, and the hepatocellular enzymatic activity on hepatic drug clearance

  • K. PangM. Rowland
  • Biology, Medicine
    Journal of Pharmacokinetics and Biopharmaceutics
  • 2005
Although both models predict similar hepatic drug clearances under a variety of conditions, marked differences between them become apparent in their predictions of the influence of changes in the determinants of drug clearance on various pharmacokinetic parameters.

Flutamide and cyproterone acetate exert agonist effects: induction of androgen receptor-dependent neuroprotection.

It is observed that, although flutamide and cyproterone acetate blocked androgen-induced gene expression, they failed to inhibit DHT protection against apoptotic insults in cultured hippocampal neurons, suggesting a role for AR in the agonist effects of antiandrogens.

Androgen receptor coactivators lysine-specific histone demethylase 1 and four and a half LIM domain protein 2 predict risk of prostate cancer recurrence.

This study correlated expression patterns of the androgen receptor (AR) coactivators lysine-specific histone demethylase 1 (LSD1) and four and a half LIM-domain protein 2 (FHL2) and pointed to a role of LSD1 and FHL2 in constitutive activation of AR-mediated growth signals.