A Pilot Study to Assess Adenosine 5'-triphosphate Metabolism in Red Blood Cells as a Drug Target for Potential Cardiovascular Protection.

Objective: To study the effect of exercise preconditioning on adenosine 5'triphosphate (ATP) metabolism in red blood cells and cardiovascular protection against injury induced by isoproterenol in vivo.

Methods: Male Sprague Dawley rats (SDR) were each exercised on a treadmill for 15 minutes at 10 m/min and 10% grade (n = 7) (LowEx), or 14 m/min and 22% grade (n = 8) (VigEx). Two hours after the exercise, each rat received a single dose of isoproterenol (30 mg/kg) by subcutaneous (sc) injection.

Diltiazem reduces mortality and breakdown of ATP in red blood cell induced by isoproterenol in a freely moving rat model in vivo.

The benefit of calcium channel blockers for cardiovascular prevention against heart attack and stroke has not been firmly supported. We investigated the possible cardiovascular protective effect of diltiazem (DTZ) against injury induced by isoproterenol using a freely moving rat model in vivo. Sprague Dawley rats were injected subcutaneously (sc) with either 5 or 10 mg/kg of DTZ, or saline as control, twice daily for five doses.

Effect of acute exercise on cardiovascular hemodynamic and red blood cell concentrations of purine nucleotides in hypertensive compared with normotensives rats.

Objective: The mechanisms of exercise-induced health benefits are complex and not fully understood. This study investigated the effects of exercise and hypertension on cardiovascular hemodynamic responses and red blood cell (RBC) concentrations of purine nucleotides using normotensive and hypertensive rat models in vivo.

Methods: Sprague Dawley rats (SDRs) and spontaneously hypertensive rats (SHRs) were exercised on a treadmill for 15 min at a speed of 10 m/min and 5% grade.

Comparing pharmacokinetics and metabolism of diltiazem in normotensive Sprague Dawley and Wistar Kyoto rats vs. spontaneously hypertensive rats in vivo.

Background: In order to identify a suitable rodent model for preclinical study of calcium antagonists, the pharmacokinetics and metabolism of one of the prototypes diltiazem (DTZ) in normotensive Sprague Dawley (SDR) was compared with Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) following 5 mg/kg twice daily for five doses given by subcutaneous injection.

Methods: Pharmacokinetic data were analyzed by standard procedures assuming a one-compartment model with first-order input using Rstrips(®), and differences between the groups were considered significant when p<0.05.

Exercise improves hemodynamic profiles and increases red blood cell concentrations of purine nucleotides in a rodent model.

Objective: To study the effect of exercise on hemodynamic profiles and red blood cell (RBC) concentrations of adenosine-5'-triphosphate (ATP).

Methods: Male Sprague-Dawley (SD) rats (n = 9) were exercised on a treadmill for 15 min at a speed of 10 m/min with a 5% gradient after an hour settling down in a restrainer. Blood samples were collected via an indwelling carotid artery catheter using a 'Stopping Solution' from each rat before, during and after exercise.

Pharmacokinetics and metabolism of diltiazem following multiple doses: comparing normotensive rat vs. hypertensive rat models in vivo.

In order to identify a suitable rodent model for preclinical study of calcium antagonists, pharmacokinetics and metabolism of diltiazem (DTZ) were compared in normotensive SD and hypertensive SHR rat models following multiple doses (5 mg/kg twice daily for 5 doses). Plasma concentrations of DTZ and its major metabolites appeared to be higher in the SHR than the SD rats, although the differences did not reach statistical significance (p > 0.05).

Pharmacokinetics of cladribine in a rat model following subcutaneous and intra-arterial injections.

Male Sprague Dawley rats (n = 6-8 per group) weighing from 300-450 g were used for the study. Each rat received a single dose of cladribine (CdA) by ia (1 mg/kg) or s.c.

Development and validation of a sensitive and specific HPLC assay of cladribine for pharmacokinetics studies in rats.

Purpose: To develop and validate a sensitive and specific HPLC assay for cladribine (CdA) in plasma for pharmacokinetic studies in rats.

Methods: CdA and the internal standard AZT were purchased from Sigma-Aldrich Chem. The HPLC system consisted of a Shimadzu LC-9A pump, a 3 im, 250 x 2.

Pharmacokinetics and metabolism of diltiazem in rats: comparing single vs repeated subcutaneous injections in vivo.

The objective of the study was to determine the effect of repeated administration on the pharmacokinetics and metabolism of diltiazem (DTZ) using an in vivo rat model. Male SD rats (n = 6-10 per group) weighing 350-450 g were used. Each rat received either a single 20 mg/kg dose of DTZ by subcutaneous (s.

Exercise hemodynamic and neurohormone responses as sensitive biomarkers for diltiazem in rats.

Purpose: To investigate the potential of exercise hemodyanamic and neurohormone variables as sensitive biomarkers for pre-clinical evaluation of diltiazem (DTZ).

Methods: Sprague Dawley (SD) rats were randomly divided into 3 groups (n = 6 - 8 each), and each group received DTZ 10 mg/kg twice daily for 5 doses or saline followed by a treadmill exercise protocol for 7 min with speed set at 7 m/min at 3 % grade. The 3rd group received saline but no exercise.

Biomarker World Congress 2005.

This report covers some of the many excellent talks, and a selected number of posters, that were presented at this conference. It includes several emerging issues in biomarker development and the question of how biomarker science can drive targeted drug discovery and development and form a scientific basis for personalized medicine. Although relatively small, the meeting provided a good opportunity for business networking, particularly for those involved in the development and regulation of medical diagnostics and biopharmaceuticals.

DP-b99 (D-Pharm).

DP-b99 is a derivative of the calcium chelator BAPTA that is under development as a neuroprotectant for the potential treatment of stroke, head trauma and neurological damage associated with coronary artery bypass graft. By March 2003, phase II clinical trials in acute stroke and traumatic brain injury were ongoing.

Technology evaluation: GEM-231, Hybridon.

GEM-231 (HYBO-165) is an 18mer hybrid oligonucleotide under development by Hybridon for the potential treatment of cancer. Phase I/II dose-escalation trials of GEM-231 in combination with paclitaxel and docetaxel were ongoing in March 2002. At this time, a phase I/II trial of GEM-231 in combination with irinotecan (CPT-11) was initiated in patients with solid tumors.