The pharmacology and subacute toxicology of dopamine.

Preclinical studies with dopamine showed a unique spectrum of biological activities which suggested that it might be of therapeutic use in the clinical syndromes of shock and low cardiac output. Most prominent among these were its effects on cardiac output, renal perfusion, and vital organ flow. The unique effect on renal function and the subsequent studies by Goldberg and his colleagues led to the recognition of a previously unknown catecholamine receptor site, the 'dopaminergic receptor'. Studies on the toxicology of dopamine in our laboratories suggested that dopamine could be safely used in the clinic.

Effect of temperature on binding of warfarin by human serum albumin.

The in vitro binding of warfarin by human serum albumin was studied at various temperatures and at pH 7.4 by a frontal gel filtration technique. The results can be best described in terms of a two class-of-binding site model, in which the numbers of primary and secondary sites are constrained to the average values for all experiments (n1 = 1.38 and n2 = 3.73). Analysis of the temperature dependence of the binding yielded the following thermodynamic parameters: deltaH1 =-2.55 kcal/mole, deltaS1=16.1 eu, and deltaF1=-7.34 kcal/mole for the primary binding and deltaH2=-5.08 kcal/mole, deltaS2=-1.10 eu, and deltaF2=4.72 kcal/mole for the secondary binding. Calculations based on these results showed that, for the therapeutic concentration range, warfarin was over 99% bound to albumin present in physiological concentration. These findings are compared and contrasted to binding data in the literature for warfarin and salicylate.

Intropin (dopamine hydrochloride) intravenous admixture compatibility. Part 2: stability with some commonly used antibiotics in 5% dextrose injection.

The stability of dopamine hydrochloride (Intropin) and several commonly used antibiotics was studied as admixtures in 5% Dextrose Injection USP. The antibiotic-dopamine-dextrose 5% admixtures were assayed for dopamine by colorimetric and chromatographic procedures. The antibiotics were assayed by standard microbiological methods. Kanamycin sulfate, tetracycline hydrochloride, carbenicillin disodium and chloramphenicol sodium succinate were stable in the Intropin-5% dextrose admixture for a period of 24 hours at room temperature in fluorescent and natural (western exposure) light. Gentamicin sulfate, penicillin G potassium and cephalothin sodium were stable in Intropin-5% dextrose admixture for six hours. Ampicillin sodium was stable in the Intropin admixture for only one hour. Amphotericin B was physically unstable in the Intropin-dextrose 5% solution upon admixture. The potency of dopamine hydrochloride remained substantially unchanged in the presence of the above antibiotics. It is recommended that dopamine not be added to amphotericin B or ampicillin sodium admixtures. Further, in order to avoid a fixed combination of potent drugs, it is recommended that a "piggyback" administration set or administration into a second injection site be employed when another drug is to be administered with dopamine hydrochloride.

Intropin (dopamine hydrochloride) intravenous admixture compatibility. Part 1: stability with common intravenous fluids.

The stability of dopamine hydrochloride (Intropin) in several large-volume parenteral solutions was studied. Admixtures of dopamine were assayed by colorimetric and chromatographic procedures. Admixtures (800 mug dopamine per ml) in the following intravenous fluids in glass bottles at pH 6.85 or below were found to be chemically and physically stable for at least 48 hours at room temperature: dextrose 5%, dextrose 5% and sodium chloride 0.9%, 5% dextrose in 0.45% sodium chloride, dextrose 5% in lactated Ringer's solution, lactated Ringer's injection, 0.9% sodium chloride, 1/6 molar sodium lactate, and 20% mannitol. The admixture of dopamine in 5% dextrose was stable for a minimum of seven days at 5 C. A 5% dextrose-dopamine admixture in a polyvinylchloride bag was stable for at least 24 hours at room temperature. The admixture of dopamine in 5% sodium bicarbonate solution produced an unstable solution of pH 8.20. A chemical and physical change (development of a pink color) was observed in this admixture. It is recommended that dopamine not be added to 5% sodium bicarbonate solution or any alkaline intravenous solution.