Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Atenolol: a Cardiovascular Safety Pharmacology Study Including Ventricular Contractility Using Radiotelemetry in Conscious Beagle Dogs Following Oral Administration

ABSTRACT: Radiotelemetry in n=4 male Conscious Beagle Dogs, dosed with atenolol at 10, 30 and 90 mg/kg po. No PK phase. Parameters measured: haemodynamic parameters (SAP, DAP, MAP, HR, LVEDP, TPR, CO, SV) and ECG parameters (RR, PR, QRS, QT, QTcF and QTcb intervals). Cardiovascular function (arterial blood pressure and electrocardiogram), body temperature and physical activity were recorded continuously for a period of at least 60 minutes before each dosing and for at least 24 hours following each dosing relative to dosing.

ORGANISM(S): Beagle dogs

SUBMITTER:

PROVIDER: S-TQST57 | biostudies-other |

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Sotalol: a cardiovascular safety pharmacology study using radiotelemetry in conscious beagle dogs following oral administration

Project description: Not available

| S-TQST64 | biostudies-other

Moxifloxacin: A Cardiovascular and Respiratory Safety Pharmacology Study Using Radiotelemetry in Conscious Beagle Dogs Following Oral Administration

Project description: Not available

| S-TQST68 | biostudies-other

Atenolol: haemodynamic effects of atenolol in chronically-instrumented conscious dogs.

Project description: Not available

| S-TQST56 | biostudies-other

Clozapine: cardiovascular Effects in Conscious, Telemetered Beagle Dogs

Project description: Not available

| S-TQST58 | biostudies-other

Moxifloxacin: Cardiovascular Effects of Moxifloxacin in Conscious, Telemetered Beagle Dogs

Project description: Not available

| S-TQST59 | biostudies-other

Sotalol: Cardiovascular Effects of sotalol in Conscious, Telemetered Beagle Dogs

Project description: Not available

| S-TQST63 | biostudies-other

Safety studies on intravenous administration of oncolytic recombinant vesicular stomatitis virus in purpose-bred beagle dogs.

Project description:VSV-IFN?-NIS is a novel recombinant oncolytic vesicular stomatitis virus (VSV) with documented efficacy and safety in preclinical murine models of cancer. To facilitate clinical translation of this promising oncolytic therapy in patients with disseminated cancer, we are utilizing a comparative oncology approach to gather data describing the safety and efficacy of systemic VSV-IFN?-NIS administration in dogs with naturally occurring cancer. In support of this, we executed a dose-escalation study in purpose-bred dogs to determine the maximum tolerated dose (MTD) of systemic VSV-hIFN?-NIS, characterize the adverse event profile, and describe routes and duration of viral shedding in healthy, immune-competent dogs. The data indicate that an intravenous dose of 10(10) TCID50 is well tolerated in dogs. Expected adverse events were mild to moderate fever, self-limiting nausea and vomiting, lymphopenia, and oral mucosal lesions. Unexpected adverse events included prolongation of partial thromboplastin time, development of bacterial urinary tract infection, and scrotal dermatitis, and in one dog receiving 10(11) TCID50 (10 × the MTD), the development of severe hepatotoxicity and symptoms of shock leading to euthanasia. Viral shedding data indicate that detectable viral genome in blood diminishes rapidly with anti-VSV neutralizing antibodies detectable in blood as early as day 5 postintravenous virus administration. While low levels of viral genome copies were detectable in plasma, urine, and buccal swabs of dogs treated at the MTD, no infectious virus was detectable in plasma, urine, or buccal swabs at any of the doses tested. These studies confirm that VSV can be safely administered systemically in dogs, justifying the use of oncolytic VSV as a novel therapy for the treatment of canine cancer.

| S-EPMC4124537 | biostudies-literature

Pharmacokinetics and Safety of Mitragynine in Beagle Dogs.

Project description:Mitragynine is the most abundant psychoactive alkaloid derived from the leaves of Mitragyna speciosa (kratom), a tropical plant indigenous to regions of Southeast Asia. Mitragynine displays a moderate affinity to opioid receptors, and kratom is often self-prescribed to treat pain and/or opioid addiction. The purpose of this study was to investigate the safety and pharmacokinetic properties of mitragynine in the dog. Single dose oral (5 mg/kg) and intravenous (0.1 mg/kg) pharmacokinetic studies of mitragynine were performed in female beagle dogs. The plasma concentrations of mitragynine were measured using ultra-performance liquid chromatography coupled with a tandem mass spectrometer, and the pharmacokinetic properties were analyzed using non-compartmental analysis. Following intravenous administration, mitragynine showed a large volume of distribution (Vd, 6.3 ± 0.6 L/kg) and high clearance (Cl, 1.8 ± 0.4 L/h/kg). Following oral mitragynine dosing, first peak plasma (Cmax, 278.0 ± 47.4 ng/mL) concentrations were observed within 0.5 h. A potent mu-opioid receptor agonist and active metabolite of mitragynine, 7-hydroxymitragynine, was also observed with a Cmax of 31.5 ± 3.3 ng/mL and a Tmax of 1.7 ± 0.6 h in orally dosed dogs while its plasma concentrations were below the lower limit of quantification (1 ng/mL) for the intravenous study. The absolute oral bioavailability of mitragynine was 69.6%. Administration of mitragynine was well tolerated, although mild sedation and anxiolytic effects were observed. These results provide the first detailed pharmacokinetic information for mitragynine in a non-rodent species (the dog) and therefore also provide significant information for allometric scaling and dose predictions when designing clinical studies.

| S-EPMC7907416 | biostudies-literature

Safety studies and viral shedding of intramuscular administration of oncolytic vaccinia virus TG6002 in healthy beagle dogs.

Project description:BackgroundCancer is a leading cause of mortality for both humans and dogs. As spontaneous canine cancers appear to be relevant models of human cancers, developing new therapeutic approaches could benefit both species. Oncolytic virotherapy is a promising therapeutic approach in cancer treatment. TG6002 is a recombinant oncolytic vaccinia virus deleted in the thymidine kinase and ribonucleotide reductase genes and armed with the suicide gene FCU1 that encodes a protein which catalyses the conversion of the non-toxic 5-fluorocytosine into the toxic metabolite 5-fluorouracil. Previous studies have shown the ability of TG6002 to infect and replicate in canine tumor cell lines, and demonstrated its oncolytic potency in cell lines, xenograft models and canine mammary adenocarcinoma explants. Moreover, 5-fluorouracil synthesis has been confirmed in fresh canine mammary adenocarcinoma explants infected with TG6002 with 5-fluorocytosine. This study aims at assessing the safety profile and viral shedding after unique or repeated intramuscular injections of TG6002 in seven healthy Beagle dogs.ResultsRepeated intramuscular administrations of TG6002 at the dose of 5 × 107 PFU/kg resulted in no clinical or biological adverse effects. Residual TG6002 in blood, saliva, urine and feces of treated dogs was not detected by infectious titer assay nor by qPCR, ensuring the safety of the virus in the dogs and their environment.ConclusionsThese results establish the good tolerability of TG6002 in healthy dogs with undetectable viral shedding after multiple injections. This study supports the initiation of further studies in canine cancer patients to evaluate the oncolytic potential of TG6002 and provides critical data for clinical development of TG6002 as a human cancer therapy.

| S-EPMC7446062 | biostudies-literature

Moxifloxacin: A Cardiovascular Safety Pharmacology Study Using Radiotelemetry in Conscious Cynomolgus Monkeys Following Oral Administration

Project description: Not available

| S-TQST84 | biostudies-other