Proteoz Actions

How long did you take this medication to work?
sponsored

Actions of Proteoz in details

The action of the drug on the human body is called Pharmacodynamics in Medical terminology. To produce its effect and to change the pathological process that is happening the body and to reduce the symptom or cure the disease, the medicine has to function in a specific way. The changes it does to the body at cellular level gives the desired result of treating a disease. Drugs act by stimulating or inhibiting a receptor or an enzyme or a protein most of the times. Medications are produced in such a way that the ingredients target the specific site and bring about chemical changes in the body that can stop or reverse the chemical reaction which is causing the disease.
sponsored

Proteoz is a reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome in mammalian cells. The 26S proteasome is a large protein complex that degrades ubiquitinated proteins. The active site of the proteasome has chymotrypsin-like, trypsin-like, and postglutamyl peptide hydrolysis activity. The 26S proteasome degrades various proteins critical to cancer cell survival, such as cyclins, tumor suppressors, BCL-2, and cyclin-dependent kinase inhibitors. Inhibition of these degradations sensitizes cells to apoptosis. Proteoz is a potent inhibitor of 26S proteasome, which sensitizes activity in dividing multiple myeloma and leukemic cells, thus inducing apoptosis. In addition, Proteoz appears to increase the sensitivity of cancer cells to traditional anticancer agents (e.g., gemcitabine, cisplatin, paclitaxel, irinotecan, and radiation).

How should I take Proteoz?

Before receiving Proteoz, make sure you understand all the risks and benefits. It is important for you to work closely with your doctor during your treatment.

You will receive Proteoz while you are in a hospital or cancer treatment center. A nurse or other trained health professional will give you Proteoz. Proteoz is given through a needle placed in one of your veins or as a shot under your skin (usually in the abdomen or thighs).

You may also receive medicines to help prevent nausea, vomiting, or diarrhea. Ask your doctor or other health caregiver if you should drink extra water while you are using Proteoz. This could help you avoid feeling dizzy or lightheaded.

If you are using Proteoz for multiple myeloma, it is important to tell your doctor if you have received Proteoz in the past.

Proteoz administration

Administration of drug is important to know because the drug absorption and action varies depending on the route and time of administration of the drug. A medicine is prescribed before meals or after meals or along with meals. The specific timing of the drug intake about food is to increase its absorption and thus its efficacy. Few work well when taken in empty stomach and few medications need to be taken 1 or 2 hrs after the meal. A drug can be in the form of a tablet, a capsule which is the oral route of administration and the same can be in IV form which is used in specific cases. Other forms of drug administration can be a suppository in anal route or an inhalation route.
sponsored

Note: The reconstituted concentrations for IV and SubQ administration are different; use caution when calculating the volume for each route and dose. Consider SubQ administration in patients with preexisting or at high risk for peripheral neuropathy.

IV: Administer via rapid IV push (3 to 5 seconds). When administering in combination with rituximab for first-line therapy of mantle cell lymphoma, administer Proteoz prior to rituximab.

SubQ (Velcade only): Subcutaneous administration of Proteoz 1.3 mg/m days 1, 4, 8, and 11 of a 21-day treatment cycle has been studied in a limited number of patients with relapsed multiple myeloma; doses were administered subcutaneously (concentration of 2.5 mg/mL) into the thigh or abdomen, rotating the injection site with each dose; injections at the same site within a single cycle were avoided (Moreau 2010; Moreau 2011). Response rates were similar to IV administration; decreased incidence of grade 3 or higher adverse events were observed with SubQ administration. Administer at least 1 inch from an old site and never administer to tender, bruised, erythematous, or indurated sites. If injection site reaction occurs, the more dilute 1 mg/mL concentration may be used SubQ (or IV administration of 1 mg/mL concentration may be considered).

For SubQ (Velcade) or IV administration only; fatalities have been reported with inadvertent intrathecal administration. Proteoz should NOT be delivered to the patient at the same time with any medications intended for central nervous system administration.

Note: The generic product (Fresenius Kabi) is NOT approved for subcutaneous administration.

Proteoz pharmacology

Pharmacokinetics of a drug can be defined as what body does to the drug after it is taken. The therapeutic result of the medicine depends upon the Pharmacokinetics of the drug. It deals with the time taken for the drug to be absorbed, metabolized, the process and chemical reactions involved in metabolism and about the excretion of the drug. All these factors are essential to deciding on the efficacy of the drug. Based on these pharmacokinetic principles, the ingredients, the Pharmaceutical company decides dose and route of administration. The concentration of the drug at the site of action which is proportional to therapeutic result inside the body depends on various pharmacokinetic reactions that occur in the body.
sponsored

Mechanism of Action

Proteoz is a reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome in mammalian cells. The 26S proteasome is a large protein complex that degrades ubiquitinated proteins. The ubiquitin- proteasome pathway plays an essential role in regulating the intracellular concentration of specific proteins, thereby maintaining homeostasis within cells. Inhibition of the 26S proteasome prevents this targeted proteolysis, which can affect multiple signaling cascades within the cell. This disruption of normal homeostatic mechanisms can lead to cell death. Experiments have demonstrated that Proteoz is cytotoxic to a variety of cancer cell types in vitro. Proteoz causes a delay in tumor growth in vivo in nonclinical tumor models, including multiple myeloma.

Pharmacodynamics

Following twice weekly administration of 1 mg/m2 and 1.3 mg/m2 Proteoz doses (n=12 per each dose level), the maximum inhibition of 20S proteasome activity (relative to baseline) in whole blood was observed 5 minutes after drug administration. Comparable maximum inhibition of 20S proteasome activity was observed between 1 and 1.3 mg/m2 doses. Maximal inhibition ranged from 70% to 84% and from 73% to 83% for the 1 mg/m2 and 1.3 mg/m2 dose regimens, respectively.

Pharmacokinetics

Following intravenous administration of 1 mg/m2 and 1.3 mg/m2 doses, the mean maximum plasma concentrations of Proteoz (Cmax) after the first dose (Day 1) were 57 and 112 ng/mL, respectively. When administered twice weekly, the mean maximum observed plasma concentrations ranged from 67 to 106 ng/mL for the 1 mg/m2 dose and 89 to 120 ng/mL for the 1.3 mg/m2 dose.

Distribution:

The mean distribution volume of Proteoz ranged from approximately 498 to 1884 L/m2 following single- or multiple-dose administration of 1 mg/m2 or 1.3 mg/m2.

The binding of Proteoz to human plasma proteins averaged 83% over the concentration range of 100 to 1,000 ng/mL.

Elimination:

The mean elimination half-life of Proteoz after multiple dosing ranged from 40 hours to 193 hours after the 1 mg/m2 dose and 76 hours to 108 hours after the 1.3 mg/m2 dose. The mean total body clearances was 102 L/h and 112 L/h following the first dose for doses of 1 mg/m2 and 1.3 mg/m2, respectively, and ranged from 15 L/h to 32 L/h following subsequent doses for doses of 1 and 1.3 mg/m2, respectively.

Metabolism: The major metabolic pathway is deboronation to form two deboronated metabolites that subsequently undergo hydroxylation to several metabolites. Deboronated Proteoz metabolites are inactive as 26S proteasome inhibitors. Pooled plasma data from 8 patients at 10 min and 30 min after dosing indicate that the plasma levels of metabolites are low compared to the parent drug.

In vitro studies indicate that Proteoz is primarily oxidatively metabolized via cytochrome P450 enzymes 3A4, 2C19, and 1A2.

Excretion: The pathways of elimination of Proteoz have not been characterized in humans.

Specific Populations:

Age: Analyses of data after the first dose of Cycle 1 (Day 1) in patients who had received intravenous doses of 1 mg/m2 and 1.3 mg/m2 showed that both dose-normalized AUC and Cmax tend to be less in younger patients. Patients less than 65 years of age had about 25% lower mean dose-normalized AUC and Cmax than those greater than or equal to 65 years of age.

Sex: Sex has no clinically important effect on Proteoz exposure.

Hepatic Impairment: Mild hepatic impairment had no clinically important effect on dose-normalized AUC or Cmax. The dose-normalized mean AUC was increased by approximately 60% in patients with moderate hepatic impairment (defined as total bilirubin greater than 1.5 to 3 times the upper limit of normal and any AST) or severe hepatic impairment (defined as total bilirubin greater than 3 times the upper limit of normal and any AST).

Renal Impairment: Dose-normalized AUC and Cmax was comparable for patients with creatinine clearance (CLcr) from 59 mL/min/1.73 m2 to less than 20 mL/min/1.73 m2 compared to patients with CLcr greater than or equal to 60 mL/min/1.73 m2.

Drug Interaction Studies

Effect of Other Drugs on Proteoz: The coadministration of omeprazole, a strong inhibitor of CYP2C19, had no effect on the exposure of Proteoz.

The coadministration of ketoconazole, a strong CYP3A4 inhibitor, increased the exposure of Proteoz by 35%.

The coadministration of rifampin, a strong CYP3A4 inducer, is expected to decrease the exposure of Proteoz by at least 45%. Decreases greater than 45% may occur, as the drug interaction trial was not designed to evaluate the maximum effect of rifampin on Proteoz exposure.

Effect of Proteoz on Other Drugs: Proteoz inhibits CYP2C19 activity in vitro and the coadministration of Proteoz for injection with sensitive or narrow therapeutic CYP2C19 substrates may increase their exposure. Proteoz did not inhibit CYP1A2, 2C9, 2D6, or 3A4 in vitro.

Proteoz did not induce the CYP3A4 or 1A2 activity in vitro.



References

  1. DailyMed. "BORTEZOMIB: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
  2. NCIt. "Bortezomib: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
  3. EPA DSStox. "Bortezomib: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).

Reviews

The results of a survey conducted on ndrugs.com for Proteoz are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Proteoz. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.

User reports

Consumer reported administration

No survey data has been collected yet


Consumer reviews


There are no reviews yet. Be the first to write one!


Your name: 
Email: 
Spam protection:  < Type 29 here

Information checked by Dr. Sachin Kumar, MD Pharmacology

| Privacy Policy
This site does not supply any medicines. It contains prices for information purposes only.
© 2003 - 2024 ndrugs.com All Rights Reserved