Playing Hide-and-Seek with Tyrosine Kinase Inhibitors: Can We Overcome Administration Challenges?

Tyrosine kinase inhibitors (TKIs) have demonstrated significant efficacy against various types of cancers through molecular targeting mechanisms. Over the past 22 years, more than 100 TKIs have been approved for the treatment of various types of cancer indicating the significant progress achieved in this research area. Despite having significant efficacy and ability to target multiple pathways, TKIs administration is associated with challenges.

Dissolution Profiles Comparison Using Conventional and Bias Corrected and Accelerated f2 Bootstrap Approaches with Different Software's: Impact of Variability, Sample Size and Number of Bootstraps.

Dissolution profiles comparison is an important element in order to support biowaivers, scale-up and post approval changes and site transfers. Highly variable dissolution can possess significant challenges for comparison and f2 bootstrap approach can be utilized in such cases. However, availability of different types of f2 and confidence intervals (CI) methods indicates necessity to understand each type of calculation thoroughly.

An Open-Labeled Randomized Prospective Multi-center Study to Evaluate the Efficacy and Safety of Intra-articular Injection of OSSINEXT™, an Autologous Growth Factor Concentrate (AGFC) Compared to Hyaluronic Acid (HA) in Knee Osteoarthritis.

Background: Osteoarthritis (OA) is known as degenerative arthritis and is the second most common rheumatologic problem with a prevalence of 22%-39% in India. Knee OA (KOA) is a major cause of mobility impairment, particularly among females. Non-surgical treatment options for KOA include intra-articular injections of platelet-rich plasma (PRP) and hyaluronic acid (HA).

A Prospective Multicenter Study to Evaluate the Safety and Efficacy of the Topical Application of MYOWNN™, an Autologous Growth Factor Concentrate (AGFC) Serum, in Anti-Aging.

Background Growth factors from platelets have been emerging as a revolutionary treatment with the ability to induce cell growth in the skin, which results in retarding and reversing the aging process. Platelet-rich plasma (PRP) allows for greater release of growth factors and biologically active proteins, which in turn activates the cascade of stimulation of neoangiogenesis and collagen production. PRP is used in anti-aging and facial skin rejuvenation in the form of dermal injections and topical application during micro-needling.

Levonadifloxacin, a Novel Broad-Spectrum Anti-MRSA Benzoquinolizine Quinolone Agent: Review of Current Evidence.

Levonadifloxacin and its prodrug alalevonadifloxacin are novel broad-spectrum anti-MRSA agents belonging to the benzoquinolizine subclass of quinolone, formulated for intravenous and oral administration, respectively. Various in vitro and in vivo studies have established their antimicrobial spectrum against clinically significant Gram-positive, Gram-negative, atypical, and anaerobic pathogens. The potent activity of levonadifloxacin against MRSA, quinolone-resistant , and hetero-vancomycin-intermediate strains is an outcome of its well-differentiated mechanism of action involving preferential targeting to DNA gyrase.

Safety, tolerability and pharmacokinetics of oral nafithromycin (WCK4873) after single or multiple doses and effects of food on single-dose bioavailability in healthy adult subjects.

Nafithromycin (WCK 4873), a novel lactone-ketolide, was administered to healthy adult subjects in 2 randomized, double-blind, placebo-controlled, Phase 1 studies. In the first-in-human study, single-ascending oral doses of nafithromycin (100 to 1200 mg) were administered to subjects under fasted or fed condition, with effects of food on bioavailability of nafithromycin studied at the dose levels of 400 and 800 mg. In the second study, multiple-ascending oral doses of 600, 800, or 1000 mg of nafithromycin were administered once daily for 7 days under a fed condition.

Single-Center Investigation of the Pharmacokinetics of WCK 4282 (Cefepime-Tazobactam Combination) in Renal Impairment.

WCK 4282 is a combination product of cefepime (FEP) and tazobactam (TAZ) in a 1:1 ratio currently under development for the treatment of multidrug-resistant Gram-negative bacterial infections. We investigated the effect of renal impairment on the pharmacokinetics (PK) and safety of WCK 4282 in 48 subjects with various degrees of renal function. Subjects were categorized on the basis of their Cockcroft-Gault equation-estimated creatinine clearance (CL).

Single-Center Evaluation of the Pharmacokinetics of WCK 5222 (Cefepime-Zidebactam Combination) in Subjects with Renal Impairment.

WCK 5222 is a novel β-lactam-β-lactam-enhancer combination of cefepime (FEP) and zidebactam (ZID). ZID is a novel β-lactam enhancer with a dual action of binding to Gram-negative penicillin-binding protein 2 (PBP2) and β-lactamase inhibition. WCK 5222 is being developed as a new therapeutic option for the treatment of complicated multidrug-resistant Gram-negative pathogen infections.

Electrocardiographic Effects of a Supratherapeutic Dose of WCK 2349, a Benzoquinolizine Fluoroquinolone.

The purpose of this study was to measure the electrocardiographic (ECG) effects of WCK 2349 (the L-alanine ester prodrug of levonadifloxacin) at a supratherapeutic oral dose of 2,600 mg. A total of 48 healthy volunteers were randomized to treatment with placebo, WCK 2349, or oral moxifloxacin, 400 mg, in a crossover-designed thorough QT study. A supratherapeutic mean maximum levonadifloxacin concentration (C ) of 43.

Plasma and Intrapulmonary Concentrations of Cefepime and Zidebactam following Intravenous Administration of WCK 5222 to Healthy Adult Subjects.

WCK 5222 is a combination of cefepime and the novel β-lactam enhancer zidebactam being developed for the treatment of serious Gram-negative bacterial infections. The objective of this study was to compare plasma (total), epithelial lining fluid (ELF), and alveolar macrophage (AM) concentrations of cefepime and zidebactam in healthy adult subjects. The WCK 5222 dosing regimen was 2 g cefepime/1 g zidebactam administered as a 1-h intravenous infusion every 8 h for a total of 7 doses.

Comparative evaluation of pharmacokinetics and pharmacodynamics of insulin glargine (Glaritus) and Lantus in healthy subjects: a double-blind, randomized clamp study.

Aims: The objective of the study was to compare the pharmacokinetic (PK) and pharmacodynamic (PD) properties of an insulin glargine formulation, Glaritus (test) with the innovator's formulation Lantus (reference) using the euglycemic clamp technique in a single-dose, double-blind, randomized, two sequences, four-period replicate crossover study in healthy volunteers (n = 40).

Methods: Subjects received subcutaneous administration of the insulin glargine (0.4 IU/kg) formulation at two occasions for test and reference and a 20% glucose solution was infused at variable rate to maintain euglycemia for 24 h.

Intrapulmonary Pharmacokinetics of Levonadifloxacin following Oral Administration of Alalevonadifloxacin to Healthy Adult Subjects.

Alalevonadifloxacin (WCK 2349) is a novel l-alanine ester prodrug of levonadifloxacin that is being developed as an oral fluoroquinolone antibiotic. The primary objective of this study was to determine and compare plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) concentrations of levonadifloxacin following oral administration of alalevonadifloxacin to healthy adult subjects. Levonadifloxacin concentrations in plasma, ELF, and AM samples from 30 healthy subjects were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) following oral dosing of alalevonadifloxacin (1,000 mg twice daily for 5 days).

Comparison of Plasma and Intrapulmonary Concentrations of Nafithromycin (WCK 4873) in Healthy Adult Subjects.

The nafithromycin concentrations in the plasma, epithelial lining fluid (ELF), and alveolar macrophages (AM) of 37 healthy adult subjects were measured following repeated dosing of oral nafithromycin at 800 mg once daily for 3 days. The values of noncompartmental pharmacokinetic (PK) parameters were determined from serial plasma samples collected over a 24-h interval following the first and third oral doses. Each subject underwent one standardized bronchoscopy with bronchoalveolar lavage (BAL) at 3, 6, 9, 12, 24, or 48 h after the third dose of nafithromycin.

Role of p-glycoprotein expression in predicting response to neoadjuvant chemotherapy in breast cancer--a prospective clinical study.

Background: Neoadjuvant chemotherapy (NACT) is an integral part of multi-modality approach in the management of locally advanced breast cancer. It is vital to predict response to chemotherapy in order to tailor the regime for a particular patient. The prediction would help in avoiding the toxicity induced by an ineffective chemotherapeutic regime in a non-responder and would also help in the planning of an alternate regime.

Efficacy & tolerability of ondansetron compared to metoclopramide in dose dependent cisplatin-induced delayed emesis.

Background & Objectives: Delayed emesis with cisplatin is a significant problem, which is often poorly controlled with conventional antiemetics. There is a relative paucity of data on the control of delayed emesis and rather inconsistent results have been reported. The present study aimed to compare the efficacy and tolerability of ondansetron versus metoclopramide in dose related grades of cisplatin-induced delayed emesis.

Topical phenytoin for wound healing.

Oral phenytoin is used widely for the treatment of convulsive disorders and about half the patients treated develop gingival overgrowth as a side effect. The apparent stimulatory effect has prompted its assessment in wound healing. Studies have shown topical phenytoin to promote healing of decubitus ulcers, venous stasis ulcers, diabetic ulcers, traumatic wounds, burns, and leprosy trophic ulcers.

Comparison of ondansetron with metoclopramide in prevention of acute emesis associated with low dose & high dose cisplatin chemotherapy.

Background & Objectives: Nausea and vomiting remain the most distressing side effects of cancer chemotherapy. The present study aimed to study the efficacy and tolerability of ondansetron versus (vs) metoclopramide in different dose related grades of cisplatin induced acute emesis.

Methods: A total of 137 patients were enrolled and 80 completed the study.