ritonavir has been researched along with Breast-Neoplasms* in 7 studies
1 review(s) available for ritonavir and Breast-Neoplasms
1 trial(s) available for ritonavir and Breast-Neoplasms
6 other study(ies) available for ritonavir and Breast-Neoplasms
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Time above threshold plasma concentrations as pharmacokinetic parameter in the comparison of oral and intravenous docetaxel treatment of breast cancer tumors.
Prolonging the time which plasma concentrations of antimitotic drugs, such as the taxanes, exceed cytotoxic threshold levels may be beneficial for their efficacy. Orally administered docetaxel offers an undemanding approach to optimize such time above threshold plasma concentrations (t C>threshold ).. A nonsystematic literature screen was performed to identify studies reporting in-vitro half-maximal inhibitory concentration (IC 50 ) values for docetaxel. Pharmacokinetics of intravenously (i.v.) docetaxel (75 mg/m 2 ) and orally administered docetaxel (ModraDoc006) co-administered with ritonavir (r) given twice daily (30 + 20 mg concomitant with 100 mg ritonavir bis in die) were simulated using previously developed population models. T C>threshold was calculated for a range of relevant thresholds in terms of in-vitro cytotoxicity and plasma concentrations achieved after i.v. and oral administration of docetaxel. A published tumor growth inhibition model for i.v. docetaxel was adapted to predict the effect of attainment of time above threshold levels on tumor dynamics.. Identified studies reported a wide range of in vitro IC 50 values [median 0.04 µmol/L, interquartile range (IQR): 0.0046-0.62]. At cytotoxic thresholds <0.078 µmol/L oral docetaxel shows up to ~7.5-fold longer t C>threshold within each 3-week cycle for a median patient compared to i.v.. Simulations of tumor dynamics showed the increased relative potential of oral docetaxel for inhibition of tumor growth at thresholds of 0.075, 0.05 and 0.005 µmol/L.. ModraDoc006/r is superior to i.v. docetaxel 75 mg/m 2 in terms of median time above cytotoxic threshold levels <0.078 µmol/L. This may indicate superior cytotoxicity and inhibition of tumor growth compared to i.v. administration for relatively docetaxel-sensitive tumors. Topics: Administration, Oral; Antimitotic Agents; Antineoplastic Agents; Breast Neoplasms; Docetaxel; Female; Humans; Ritonavir; Taxoids | 2023 |
Prolonged SARS-CoV-2 viral shedding in patients with solid tumours and associated factors.
Topics: Adenosine Monophosphate; Aged; Alanine; Antineoplastic Agents; Antiviral Agents; Breast Neoplasms; COVID-19; COVID-19 Drug Treatment; COVID-19 Nucleic Acid Testing; COVID-19 Serological Testing; COVID-19 Serotherapy; Dexamethasone; Drug Combinations; Female; Follow-Up Studies; Glucocorticoids; Humans; Hydroxychloroquine; Immunization, Passive; Immunotherapy; Latent Infection; Lopinavir; Lung Neoplasms; Male; Molecular Targeted Therapy; Neoplasms; Proportional Hazards Models; Risk Factors; Ritonavir; SARS-CoV-2; Spain; Time Factors; Virus Shedding | 2021 |
Development of a Tumour Growth Inhibition Model to Elucidate the Effects of Ritonavir on Intratumoural Metabolism and Anti-tumour Effect of Docetaxel in a Mouse Model for Hereditary Breast Cancer.
In a mouse tumour model for hereditary breast cancer, we previously explored the anti-cancer effects of docetaxel, ritonavir and the combination of both and studied the effect of ritonavir on the intratumoural concentration of docetaxel. The objective of the current study was to apply pharmacokinetic (PK)-pharmacodynamic (PD) modelling on this previous study to further elucidate and quantify the effects of docetaxel when co-administered with ritonavir. PK models of docetaxel and ritonavir in plasma and in tumour were developed. The effect of ritonavir on docetaxel concentration in the systemic circulation of Cyp3a knock-out mice and in the implanted tumour (with inherent Cyp3a expression) was studied, respectively. Subsequently, we designed a tumour growth inhibition model that included the inhibitory effects of both docetaxel and ritonavir. Ritonavir decreased docetaxel systemic clearance with 8% (relative standard error 0.4%) in the co-treated group compared to that in the docetaxel only-treated group. The docetaxel concentration in tumour tissues was significantly increased by ritonavir with mean area under the concentration-time curve 2.5-fold higher when combined with ritonavir. Observed tumour volume profiles in mice could be properly described by the PK/PD model. In the co-treated group, the enhanced anti-tumour effect was mainly due to increased docetaxel tumour concentration; however, we demonstrated a small but significant anti-tumour effect of ritonavir addition (p value <0.001). In conclusion, we showed that the increased anti-tumour effect observed when docetaxel is combined with ritonavir is mainly caused by enhanced docetaxel tumour concentration and to a minor extent by a direct anti-tumour effect of ritonavir. Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease Models, Animal; Docetaxel; Female; Mice; Mice, Knockout; Ritonavir; Taxoids; Treatment Outcome; Tumor Burden | 2016 |
Identifying the optimal dose of ritonavir in the treatment of malignancies.
Identifying the optimal dose of ritonavir therapy overcomes the chemical resistance may exhibit in some cases due to poor prognosis of imprecise staging. Dose modeling was performed by analyzing previously published data of ritonavir cancer growth inhibition in vitro and in vivo. In-vitro 3H-Thymidine-based cell proliferation assay was performed on samples of the GL15 cell line incubated with 0, 1, 10 and 100 μ M of ritonavir. Proliferation inhibition was quantified to identify energy of the used doses as described before in earlier studies. Models involving in-vivo growth of established breast cancer tumor (MDA-MB-231), KSIMM tumor and EL4-T cell thymomas in mice were used. The effects of 40 mg/kg/day for 52 days, 30 mg/kg/day for 15 days and 8.8 mg/mouse/day for about 1 week of ritonavir in those xenograft growths respectively were monitored and quantified to identify energy of those doses as described before in earlier studies. Ritonavir demonstrated an in-vitro reduction in proliferation rate in dose dependent manner. The energy of the in-vitro influences following ritonavir therapy were perfectly correlated (r = 1) with ritonavir dose, allowed to establish an efficient energy-model with a perfect fit (R2=1) describes the energy yield by ritonavir doses, enables to administer the appropriate dose. Ritonavir had also a significant influence in-vivo on all sizes of treated tumors compared to the control animals such that the energy yield by the administered drug as derived from the energy-model was 100% identical to the induced influence in tumor energy. The in-vitro determination of inhibition to proliferation by ritonavir doses is useful to characterize the response of cancer to ritonavir therapy targeting patient-personalized cancer medicine. The molecular method of response determination by 3H-TDR incorporation and ritonavir dose-energy model are reliable to avoid chemo-resistance by identifying the optimal dosing regimens and schedules prior therapy allowing the use of much lower dose of ritonavir and thus decreases the drug side effects and risks of relapse. Topics: Analgesics; Animals; Breast Neoplasms; Cell Line, Tumor; Dose-Response Relationship, Drug; Female; Male; Mice; Mice, Inbred C57BL; Mice, Nude; Ritonavir; Xenograft Model Antitumor Assays | 2014 |
Effects of HIV protease inhibitor ritonavir on Akt-regulated cell proliferation in breast cancer.
These studies were designed to determine whether ritonavir inhibits breast cancer in vitro and in vivo and, if so, how.. Ritonavir effects on breast cancer cell growth were studied in the estrogen receptor (ER)-positive lines MCF7 and T47D and in the ER-negative lines MDA-MB-436 and MDA-MB-231. Effects of ritonavir on Rb-regulated and Akt-mediated cell proliferation were studied. Ritonavir was tested for inhibition of a mammary carcinoma xenograft.. ER-positive estradiol-dependent lines (IC50, 12-24 micromol/L) and ER-negative (IC50, 45 micromol/L) lines exhibit ritonavir sensitivity. Ritonavir depletes ER-alpha levels notably in ER-positive lines. Ritonavir causes G1 arrest, depletes cyclin-dependent kinases 2, 4, and 6 and cyclin D1 but not cyclin E, and depletes phosphorylated Rb and Ser473 Akt. Ritonavir induces apoptosis independent of G1 arrest, inhibiting growth of cells that have passed the G1 checkpoint. Myristoyl-Akt, but not activated K-Ras, rescues ritonavir inhibition. Ritonavir inhibited a MDA-MB-231 xenograft and intratumoral Akt activity at a clinically attainable serum Cmax of 22 +/- 8 micromol/L. Because heat shock protein 90 (Hsp90) substrates are depleted by ritonavir, ritonavir effects on Hsp90 were tested. Ritonavir binds Hsp90 (K(D), 7.8 micromol/L) and partially inhibits its chaperone function. Ritonavir blocks association of Hsp90 with Akt and, with sustained exposure, notably depletes Hsp90. Stably expressed Hsp90alpha short hairpin RNA also depletes Hsp90, inhibiting proliferation and sensitizing breast cancer cells to low ritonavir concentrations.. Ritonavir inhibits breast cancer growth in part by inhibiting Hsp90 substrates, including Akt. Ritonavir may be of interest for breast cancer therapeutics and its efficacy may be increased by sustained exposure or Hsp90 RNA interference. Topics: Animals; Blotting, Western; Breast Neoplasms; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cyclin D1; Cyclin-Dependent Kinases; Dose-Response Relationship, Drug; Female; HIV Protease Inhibitors; HSP90 Heat-Shock Proteins; Humans; Immunohistochemistry; Immunoprecipitation; Mammary Neoplasms, Experimental; Mice; Mice, Nude; Mutant Proteins; Proto-Oncogene Proteins c-akt; Ritonavir; Tumor Suppressor Protein p53; Xenograft Model Antitumor Assays | 2006 |
HIV protease inhibitors are inhibitors but not substrates of the human breast cancer resistance protein (BCRP/ABCG2).
Breast cancer resistance protein (BCRP) is a recently discovered ATP-binding cassette drug transporter. Hence, the full spectrum of therapeutic agents that interact with BCRP remains to be elucidated. Because human immunodeficiency virus protease inhibitors (HPIs) are well known P-glycoprotein (P-gp) substrates, and there is an overlap in substrate specificity between P-gp and BCRP, this study was performed to investigate whether HPIs are substrates and/or inhibitors of BCRP. First, the effect of HPIs on BCRP efflux activity in human embryonic kidney (HEK) cells stably expressing wild-type BCRP (482R) and its two mutants (482T and 482G) was studied by measuring intracellular mitoxantrone fluorescence using flow cytometry. We found that ritonavir, saquinavir, and nelfinavir were effective inhibitors of wild-type BCRP (482R) with IC50 values of 19.5 +/- 0.8 microM, 19.5 +/- 7.6 microM, and 12.5 +/- 4.1 microM, respectively. Ritonavir, saquinavir, and nelfinavir inhibited 482T and 482G with IC50 values that were approximately 2 times greater than that for 482R. Indinavir and amprenavir had no significant inhibition on BCRP activity. Direct efflux of radiolabeled HPIs in HEK cells was measured to determine whether the HPIs are substrates of BCRP. None of the HPIs were found to be transported by BCRP. Together, ritonavir, saquinavir, nelfinavir, indinavir, and amprenavir are not substrates for BCRP. However, ritonavir, saquinavir, and nelfinavir are effective inhibitors of the transporter. These results suggest that BCRP may play an important role in drug-drug interactions involving coadministration of the HPIs with drugs that are substrates of the transporter. Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Biological Transport; Breast Neoplasms; Cells, Cultured; Drug Resistance, Neoplasm; Gene Expression; HIV Protease Inhibitors; Humans; Indinavir; Mitoxantrone; Nelfinavir; Neoplasm Proteins; Ritonavir; Saquinavir; Tritium | 2004 |