A Pharmacokinetic Study of the Interaction Between Regorafenib and Paracetamol in Male Rats.

: In clinical practice, the prevalent problem of polypharmacy could result in increased risks of drug-drug interactions. Regorafenib (REG) is commonly co-administered with paracetamol (PA) as a treatment protocol in cancer patients with pain therapy. : This study aimed to demonstrate the effect of paracetamol on the pharmacokinetic parameters of regorafenib and its metabolites following a single administration of both substances in rats.

Pharmacokinetic interaction between regorafenib and atorvastatin in rats.

Background: Regorafenib is used in the treatment of colorectal cancer and hepatocellular carcinoma. Due to the co-morbidity of hyperlipidemia in these conditions, statins, including atorvastatin, are used as potential adjuvant therapy agents. Both regorafenib and atorvastatin are metabolized by CYP3A4.

Bidirectional pharmacokinetic drug interactions between olaparib and metformin.

Objective: Olaparib is a PARP (poly-ADP-ribose polymerase) inhibitor used for maintenance therapy in BRCA-mutated cancers. Metformin is a first-choice drug used in the treatment of type 2 diabetes. Both drugs are commonly co-administered to oncologic patients with add-on type 2 diabetes mellitus.

Pharmacokinetic Drug Interaction Study of Sorafenib and Morphine in Rats.

A combination of the tyrosine kinase inhibitor-sorafenib-and the opioid analgesic-morphine-can be found in the treatment of cancer patients. Since both are substrates of P-glycoprotein (P-gp), and sorafenib is also an inhibitor of P-gp, their co-administration may affect their pharmacokinetics, and thus the safety and efficacy of cancer therapy. Therefore, the aim of this study was to evaluate the potential pharmacokinetic drug-drug interactions between sorafenib and morphine using an animal model.

The Influence of Paracetamol on the Penetration of Sorafenib and Sorafenib N-Oxide Through the Blood-Brain Barrier in Rats.

Background And Objective: Sorafenib is an oral, multikinase inhibitor with established single-agent activity in several tumor types. Sorafenib was moderately transported by P-glycoprotein (P-gp) and more efficiently by breast cancer resistance protein. The constitutive androstane receptor (CAR) is a ligand-activated transcription factor involved in P-gp regulation in the brain microvasculature.

In vivo assessment of potential for UGT-inhibition-based drug-drug interaction between sorafenib and tapentadol.

Sorafenib (SR) is one of the most potent UGT (1A1, 1A9) inhibitors (in in vitro tests). The inhibition of UGT1A1 may cause hyperbilirubinaemia, whereas the inhibition of UGT1A9 and 1A1 may result in drug-drug interactions (DDIs). Tapentadol (TAP) is a synthetic μ-opioid agonist and is used to treat moderate to severe acute pain.

Pharmacokinetic Interaction between Sorafenib and Atorvastatin, and Sorafenib and Metformin in Rats.

The tyrosine kinase inhibitor sorafenib is the first-line treatment for patients with hepatocellular carcinoma (HCC), in which hyperlipidemia and type 2 diabetes mellitus (T2DM) may often coexist. Protein transporters like organic cation (OCT) and multidrug and toxin extrusion (MATE) are involved in the response to sorafenib, as well as in that to the anti-diabetic drug metformin or atorvastatin, used in hyperlipidemia. Changes in the activity of these transporters may lead to pharmacokinetic interactions, which are of clinical significance.

In vivo assessment of the drug interaction between sorafenib and paracetamol in rats.

Purpose: Sorafenib is a multi-targeted tyrosine kinase inhibitor (TKI) used for the treatment of advanced renal cell carcinoma, hepatocellular carcinoma and radioactive iodine resistant thyroid carcinoma. Neoplastic diseases are the cause of pain, which may occur regardless of the stage of the disease. Paracetamol is a non-opioid analgesic used alone or in combination with opioids for the treatment of cancer pain.

The oxidation and hypoglycaemic effect of sorafenib in streptozotocin-induced diabetic rats.

Background: Diabetes reduces the activity of CYP3A4 and may increase the exposure for the drugs metabolized by the isoenzyme. Sorafenib is a multi-targeted tyrosine kinase inhibitor (TKI), used for the treatment of advanced renal cell carcinoma, hepatocellular carcinoma and radioactive iodine resistant thyroid carcinoma. The TKI undergoes CYP3A4-dependent oxidative transformation, which may be influenced by hyperglycaemia.

The influence of the coadministration of the p-glycoprotein modulator elacridar on the pharmacokinetics of lapatinib and its distribution in the brain and cerebrospinal fluid.

Background Lapatinib is a small-molecule tyrosine kinase inhibitor of human epidermal receptor 2 (HER2) and EGFR that has currently been approved for the treatment of HER2-positive advanced and metastatic breast cancer (BC). The ATP-binding cassette (ABC) family of transporters includes P-glycoprotein (P-gp; ABCB1) and breast cancer resistance protein (BCRP; ABCG2), which substantially restrict the penetration of drugs, including chemotherapeutics, through the blood-brain barrier and blood-cerebrospinal fluid barrier. The aim of this study was to investigate the effects of elacridar, an ABCB1 and ABCG2 inhibitor, on the brain and cerebrospinal fluid uptake of lapatinib.

The Influence of Diabetes Mellitus on Glucuronidation and Sulphation of Paracetamol in Patients with Febrile Neutropenia.

Background And Objectives: Numerous studies have confirmed the influence of diabetes mellitus on the pharmacokinetics of drugs. Paracetamol (APAP) is an antipyretic that is commonly used in febrile neutropenia (FN) therapy. APAP is chiefly metabolised by glucuronidation and sulphation.

THE EFFECT OF TOTAL AND PARTIAL NEPHRECTOMY ON THE PHARMACOKINETICS OF INTRAVENOUS PARACETAMOL IN HUMANS.

Paracetamol is one of the most common analgesic and antipyretic drugs. Recently intravenous paracetamol has been widely used to treat moderate postoperative pain. Surgery is the main method of treatment of renal cancer.

A pharmacokinetic study on lapatinib in type 2 diabetic rats.

Background: Diabetes mellitus (DM) is a complex metabolic disorder which affects the function of numerous tissues and alters the pharmacokinetic parameters of many drugs. As many oncological patients are diabetics, it is important to determine the influence of this chronic disease on the pharmacokinetics (PK) of anticancer drugs. Lapatinib is a tyrosine kinase inhibitor (TKI), approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.

The concomitant use of lapatinib and paracetamol - the risk of interaction.

Lapatinib is a tyrosine kinase inhibitor used for the treatment of breast cancer. Paracetamol is an analgesic commonly applied to patients with mild or moderate pain and fever. Cancer patients are polymedicated, which involves high risk of drug interactions during therapy.

Pharmacokinetic drug-drug interaction between erlotinib and paracetamol: A potential risk for clinical practice.

Background: Erlotinib is a tyrosine kinase inhibitor available for the treatment of non-small cell lung cancer. Paracetamol is an analgesic agent, commonly used in cancer patients. Because these drugs are often co-administered, there is an increasing issue of interaction between them.

The pharmacokinetics of oral ketoprofen in patients after gastric resection.

Background: Total and partial gastric resection may affect the pharmacokinetics of drugs, especially orally administered a few days after surgery. Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID) broadly used to treat postoperative pain, including patients after gastric resection. The aim of the research was to analyse the pharmacokinetics (PK) of orally administered ketoprofen in patients after gastrectomy.

Ocular disposition of treosulfan and its active epoxy-transformers following intravenous administration in rabbits.

Treosulfan (TREO) has an established position in chemotherapy of advanced ovarian cancer but has been also applied in uveal melanoma patients. Moreover, it is used as an orphan drug for a myeloablative conditioning prior to stem cell transplantation. In this paper, biodistribution of prodrug TREO and its active monoepoxide (S,S-EBDM) and diepoxide (S,S-DEB) into aqueous humor of the eye was studied for the first time.

Influence of the Time of Intravenous Administration of Paracetamol on its Pharmacokinetics and Ocular Disposition in Rabbits.

Background And Objectives: Paracetamol is one of the most common analgesics and antipyretics applied in health care. The aim of the study was to investigate the influence of the time-of-day administration on the paracetamol pharmacokinetics and its penetration into aqueous humour (AH).

Methods: Rabbits were divided into three groups: I-receiving paracetamol at 08.

The alteration of pharmacokinetics of erlotinib and OSI420 in type 1 diabetic rabbits.

Background: Alterations in blood glucose levels observed in diabetes, may change the pharmacokinetics of co-administered drugs and in consequence, the efficacy and safety of therapy. Many oncological patients are diabetics and it is important to determine the interaction of anticancer drugs with this chronic disease. Erlotinib is a tyrosine kinase inhibitor (TKI), approved for the treatment of patients with non-small-cell lung cancer and pancreatic cancer in combination with gemcitabine.

Pharmacokinetics of paracetamol in patients with chronic pancreatitis.

Background: Chronic pancreatitis (CP) is a progressive, irreversible disease causing damage of the gland. Abdominal pains are a typical symptom of pancreatitis both in the chronic and acute form. Paracetamol is one of analgesics used for treating mild or moderate pain.

Formation Rate-Limited Pharmacokinetics of Biologically Active Epoxy Transformers of Prodrug Treosulfan.

A prodrug treosulfan (TREO) is being evaluated in clinical trials as a myeloablative agent before hematopoietic stem cell transplantation. The active derivatives of TREO, monoepoxide (EBDM), and diepoxide (DEB) are formed in a pH-dependent nonenzymatic reaction. The aim of the study was to investigate pharmacokinetics of the TREO epoxy transformers in a rabbit model and explain the causes of low plasma concentrations of EBDM and DEB observed in patients receiving high-dose TREO before hematopoietic stem cell transplantation.

The pharmacokinetic interaction between levofloxacin and sunitinib.

Background: The aim of this study was to evaluate the impact of sunitinib on pharmacokinetics of levofloxacin. The previous study proved that levofloxacin co-administered with sunitib changes the following pharmacokinetic parameters i.e.

The pharmacokinetics and hypoglycaemic effect of sunitinib in the diabetic rabbits.

Background: Diabetes is one of the most common metabolic diseases in the world, which may influence changes in the pharmacokinetics and pharmacodynamics of drugs. Sunitinib is a tyrosine kinase inhibitor (TKI) broadly used for treatment of numerous cancers, which exhibits the side hypoglycaemic effect. The aim of the study was a comparison of concentrations and pharmacokinetics of sunitinib after a single administration in rabbits with hyperglycaemia and normoglycaemia (control group).