pazopanib and Body-Weight

In the setting of metastatic RCC (mRCC), pazopanib is approved as first line therapy. Unfortunately treatment may lead to cardiotoxicity such as hypertension, heart failure, and myocardial ischemia.. Define the in vivo role of pazopanib in the development of cardiotoxicity.. Wild type mice were dosed for 42 days via oral gavage, and separated into control and treatment (pazopanib) groups. Baseline ECG's, echocardiograms, and blood pressures were recorded. At the conclusion of the study functional parameters were again recorded, and animals were used for pathological, histological, and protein analysis.. After 2 weeks of dosing with pazopanib, the treatment group exhibited a statistically significant increase in mean arterial pressure compared to control mice (119 ± 11.7 mmHg versus 108 ± 8.2 mmHg, p = 0.049). Treatment with pazopanib led to a significant reduction in the cardiac output of mice.. Our findings in mice clearly demonstrate that treatment with pazopanib leads to a significant elevation in blood pressure after 2 weeks of dosing and this persists for the duration of dosing. The continued development of the cardio-oncology field will be paramount in providing optimal oncologic care while simultaneously improving cardiac outcomes through further investigation into the mechanisms of CV toxicity.

Topics: Angiogenesis Inhibitors; Animals; Arterial Pressure; Body Weight; Carcinoma, Renal Cell; Cardiac Output; Disease Models, Animal; Echocardiography; Electrocardiography; Heart; Hypertension; Indazoles; Kidney; Kidney Neoplasms; Mice; Myocardium; Pyrimidines; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Sulfonamides; Vascular Endothelial Growth Factor A

To determine the efficacy of pazopanib eye drops in the streptozotocin induced diabetic retinopathy rat model.. A 0.5% w/v pazopanib suspension was prepared in phosphate buffered saline (PBS, pH 7.4) in the presence of 0.5% w/v sodium carboxymethyl cellulose. Brown Norway rats were divided into three groups (n=4) - (1) healthy, (2) diabetic, and (3) diabetic with treatment. The drug suspension was administered twice daily as eye drops to group 3 for 30 days. Efficacy parameters including the number of adherent leukocytes in the retinal vasculature (leukostasis), blood-retinal FITC-dextran leakage, and vitreous-to-plasma protein ratio were measured.. Pazopanib suspension in the form of eye drops significantly reduced leukostasis (32%), FITC-dextran leakage (39%), and the vitreous-to-plasma protein ratio (64%) in diabetic animals compared to untreated diabetic group.. Pazopanib eye drops can alleviate retinal complications of diabetic retinopathy.

Topics: Administration, Ophthalmic; Animals; Blood Glucose; Blood Proteins; Blood-Retinal Barrier; Body Weight; Capillary Permeability; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Indazoles; Leukocytes; Leukostasis; Macular Edema; Male; Molecular Targeted Therapy; Ophthalmic Solutions; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Pyrimidines; Rats; Rats, Inbred BN; Sulfonamides; Time Factors; Vitreous Body