Effects of oral clotrimazole troches on the pharmacokinetics of oral and intravenous midazolam.

Aims: The aim of the study was to determine the effects of oral clotrimazole troches on the pharmacokinetics of oral and intravenous midazolam in the plasma.

Methods: We conducted a randomized, open-label, four-way crossover study in 10 healthy volunteers. Each volunteer received oral midazolam 2 mg or intravenous midazolam 0.

The pharmacokinetics of codeine and its metabolites in Blacks with sickle cell disease.

Purpose: We conducted a prospective, open-label study in 54 adult subjects with sickle cell disease to determine the relationship between morphine concentrations, cytochrome P450 (CYP) 2D6 genotype, and clinical outcomes.

Methods: A blood sample was obtained for genotyping and serial blood samples were drawn to measure codeine and its metabolites in the plasma before and after oral codeine sulfate 30 mg. Codeine and its metabolites were measured by liquid chromatography-tandem mass spectrometry (LC-MS).

Hypertension-induced renal fibrosis and spironolactone response vary by rat strain and mineralocorticoid receptor gene expression.

Introduction: Aldosterone promotes renal fibrosis via the mineralocorticoid receptor (MR), thus contributing to hypertension-induced nephropathy. We investigated whether MR gene expression influences renal fibrosis and MR antagonist response in a two-kidney, one-clip hypertensive rat model.

Materials And Methods: Brown Norway (BN), Lewis, and ACI rats were randomised to spironolactone 20 mg/kg/day or water by gavage, starting four weeks after left renal artery clipping.

Association of beta-blocker dose with serum procollagen concentrations and cardiac response to spironolactone in patients with heart failure.

Study Objective: To determine whether beta-blocker dose influences cardiac collagen turnover and the effects of spironolactone on cardiac collagen turnover in patients with heart failure.

Design: Prospective clinical study.

Setting: Two heart failure centers.

Intravenous administration of paclitaxel in Sprague-Dawley rats: what is a safe dose?

Few studies describe the administration of Taxol to rats; however, rats are typically used to study the toxicity of new drugs or novel formulations. A dose finding study was conducted to determine a safe dose of Taxol following intravenous administration in rats. Male Sprague-Dawley rats received a bolus of paclitaxel 5-20 mg/kg i.

Paclitaxel decreases the accumulation of gemcitabine and its metabolites in human leukemia cells and primary cell cultures.

Background: We identified a drug-drug interaction between gemcitabine and paclitaxel in a clinical pharmacokinetic study. The purpose of the present study was to determine whether paclitaxel affected the uptake and accumulation of the parent drug gemcitabine and the formation of its metabolites after treatment of cells with gemcitabine in vitro.

Materials And Methods: The human leukemia cell line CEM was treated with 15 micoM 3H-gemcitabine, with and without paclitaxel, and the accumulation of radiolabeled gemcitabine was assessed up to one minute and one hour.

Long-term (2-year) clinical events following transthoracic intramyocardial gene transfer of VEGF-2 in no-option patients.

Background: The short-term clinical impact of intramyocardial gene transfer (GT) of the angiogenic protein vascular endothelial growth factor-2 (VEGF-2) has been previously reported to significantly reduce Canadian Cardiovascular Society (CCS) angina class and to prolong exercise treadmill test (ETT) time. We describe the safety and long-term events (>1 year) in consecutive, nonrandomized, patients who received intramyocardial VEGF-2.

Methods: Thirty patients with intractable CCS class III or IV angina and no options for revascularization underwent direct intramyocardial GT of VEGF-2 naked DNA via limited thoracotomy at total doses of 0.