Clinical development of dopexamine hydrochloride (Dopacard) and an overview of its hemodynamic effects.

A clinical development program was initiated to identify the hemodynamic profile of activity of dopexamine hydrochloride. Studies in healthy subjects confirmed the cardiovascular activity of dopexamine hydrochloride and demonstrated its potency. Doses of 0.5 to 8 micrograms/kg/min doubled cardiac output without change in mean blood pressure, although pulse pressure did widen. In patients with stable chronic cardiac failure (mainly New York Heart Association class III), dopexamine hydrochloride (4 micrograms/kg/min) increased stroke volume 47 +/- 9%, cardiac index 64 +/- 10% and heart rate 11.7 +/- 3%. Systemic vascular resistance decreased by 42 +/- 5%. At higher doses, cardiac index increased further, but chronotropic effects became more prominent. Subsequent studies in patients recovering from cardiac surgery and studies of longer duration in patients with chronic congestive heart failure have demonstrated a similar hemodynamic profile that is sustained throughout the infusion. The renal vasodilator effects have been confirmed in both healthy subjects and patients. With all catecholamines the balance of chronotropic to inotropic or vasodilator effect is critical. Dopexamine hydrochloride (1 to 4 micrograms/kg/min) increases cardiac index by over 40% at clinically insignificant (10%) increases of heart rate.

The pharmacokinetics of nedocromil sodium, a new drug for the treatment of reversible obstructive airways disease, in human volunteers and patients with reversible obstructive airways disease.

1. The plasma concentrations and urinary excretion of nedocromil sodium have been determined following single dose administration in six healthy volunteers dosed orally (1 mg kg-1) and intravenously (0.2 microgram kg-1 for 30 min). Similar parameters were measured in six volunteers and twelve asthmatic patients dosed by inhalation (4 mg). Multiple dose kinetic measurements were also made. 2. The intravenous data demonstrated that nedocromil sodium is a high clearance drug (10.2 +/- 1.3 ml min-1 kg-1). The data were fitted by a two compartment model with very rapid elimination from the central compartment (k10 = 0.088 +/- 0.021 min-1; beta = 0.013 +/- 0.002 min-1). 81% of the dose was excreted in the urine. 3. Oral absorption was low (2-3% of the dose) and contributed negligibly to the plasma profile after inhalation. 4. After inhalation of single doses of 4 mg in volunteers and patients plasma concentration rose rapidly, plateaued and then fell monoexponentially with a half-life of approximately 2 h. The data fitted a 'flip-flop' model with two absorption components. The extent of absorption was up to 6% of the dose with less in patients. 5. After multiple dosing with 4 mg four times daily for 7 days in volunteers negligible accumulation was observed. The pattern was similar in patients treated with 4 mg four times daily after 1, 6 and 12 months.

Comparison of lung deposition of a solution after nebulization by three commonly used portable nebulizers.

The efficacy of small portable nebulizers is often assumed by patients, pharmacists and physicians. Three healthy volunteers inhaled a mixture of sodium cromoglycate solution mixed with aqueous technetium-99 nebulized by each of three nebulizers and the distribution of radioactivity was detected by gamma scintigraphy. Unexpectedly large differences in the total amount of tracer delivered to the lungs were detected. The possible mechanisms and implications are discussed but it is clear that more information on the performance of individual nebulizers should be available.

Mobility device for a child with phocomelia.

This paper describes an electric cart designed for an 11-month-old child born with multiple limb deficiencies. The device was intended to provide independently controlled mobility within the living environment and was designed to accommodate the child's growth until a commercial wheelchair would meet his mobility needs. The design provides a set of controls which can be operated by the child's partial left foot and his head. These controls are used in a manner that does not require extensive training, and which is appropriate for a child of this age.