Renal effects of the cyclooxygenase-inhibiting nitric oxide donator AZD3582 compared with rofecoxib and naproxen during normal and low sodium intake.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) and can thereby reduce renal function, especially with respect to solute excretion and renal perfusion. AZD3582 [4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl)propanoate] is a COX-inhibiting nitric oxide donator. Donation of nitric oxide by AZD3582 could preserve blood flow and thereby counteract the deleterious effects of COX inhibition in the gastrointestinal tract and possibly in other organ systems, including the kidney.

Influence of food intake on electrocardiograms of healthy male volunteers.

Objective: To study the influence of food intake on electrocardiogram (ECG) variables (heart rate, QT-, QTc-, PR-intervals, QRS-time) and morphological alterations of the T-waves in 12 healthy male volunteers.

Methods: The study was of open, three-period crossover design. On each occasion, all subjects fasted from midnight.

Determinants of furosemide delivery to its site of action.

We have investigated the pharmacokinetic determinants of delivery of furosemide to its site of action in the renal tubules in patients and healthy volunteers. The bioavailability of furosemide is low and variable. Patients with renal disease may also have a low renal extraction of furosemide.

Acute tolerance to furosemide. Pretreatment with captopril or prazosin does not influence diuresis and natriuresis.

To investigate whether the development of acute tolerance to furosemide in human subjects could be prevented or delayed by angiotensin converting enzyme inhibition or alpha 1-receptor blockade, a study was conducted on healthy volunteers. The protocol on the experimental days was identical except for pre-treatment with placebo, captopril or prazosin. During continuous furosemide infusion with urinary furosemide excretion at a constant rate, the subjects became progressively dehydrated, with a maximal decrease in plasma volume of 9-11%.