A goal of this study is to determine the contribution of intestinalcytochrome P450 3A to the observed first-pass metabolism of midazolamfollowing oral administration using simultaneous intravenous and oraladministration of midazolam and a stable isotope N-midazolam. Affectsof clarithromycin of midazolam following oral administration at theintestinal or hepatic level.
There he developed a research and clinical interest in diuretics that continues today.
This is an unblinded, random, crossover study of oral administration ofei R-ketoprofen 100mg, or racemic ketoprofen 100mg to comparepharmacokinetics and metabolite formation.
To establish the natriuretic effect, if any, of an intravenous low-dosedopamine infusion in patients with congestive heart failure.
PI's laboratoryhas had extensive interest in mechanisms of diuretic resistance whichcan be dissected by first determining changes in pharmacokinetics of adiuretic in a given clinical condition andsecondly by assessing thepharmacodynamics of response. Hislaboratory has demonstrated that aneffective method to assess pharmacodynamics is by examining therelationship between urinary excretion rate of the loop diuretic andnatriuretic response. These methods have been developed, validated, andemployed by his laboratory to define the mechanisms of diureticresistance in a variety of clinical conditions, and to develop logicaltherapeutic approaches to the patient with diuretic resistance. Thestudies currently proposed are extensions of this work. The currentproposal seeks to address the following questions concerning clinicallyrelevant issues pertaining to diuretic response: 1 Does displacement of furosemide from binding to urinary albumin inpatients with nephrotic syndrome enhance diuretic response 2 Does administration of albumin plus furosemide enhance diureticresponse in hypoalbuminemic patients with nephrotic syndrome orcirrhosis Is this effect different depending on the patient's serumalbumin concentration 3 Does ''renal dose'' dopamine enhance response to aloop diuretic inpatients with severe congestive heart failure In addition he proposes to begin a series of studies of diuretic therapy, focusing on patients with congestive heart failure CHF. Patients withCHF are common, many are heavy users of health care resources, anddiuretics are a mainstay of therapy. He proposes that decompensation ofmany patients with CHF may be due to noncompliance with diuretics andordiet. This proposal begins a long-termattempt to unravel these factorswith an ultimate goal of designing therapeutic strategies in patientswith CHF which decrease the frequency of decompensation.
Benzimidazole Analog, Cytochrome P, Drug Administration Route, Drug Interaction, Erythromycin, Gastrointestinal Drug Absorption, Genetic Polymorphism, Human Genetic Material Tag, Human Subject, Liver Metabolism, Macrolide Antibiotic, Midazolam, Muscle Relaxant, Pharmacogenetics, Pharmacokinetics, Psychopharmacology
