Disease relevance of PIROXIMONE HYDROCHLORIDE

• Therefore long-term therapy with piroximone did not appear to benefit patients with severe congestive heart failure [1].
• 14C-labelled piroximone was administered to rats at a dose of 10 mg/kg body weight [2].
• Pharmacokinetics of piroximone after oral and intravenous administration to patients with renal insufficiency [3].
• We have compared the haemodynamic effects of the imidazole derivative phosphodiesterase inhibitors enoximone and piroximone in patients with low cardiac output after cardiac surgery [4].
• Seven of the 10 patients completed 12 weeks of therapy with piroximone; one patient withdrew after 8 weeks because of deterioration in clinical status; one developed severe ventricular arrhythmias and died after 5 days of treatment; and a drug-induced hepatitis was documented in one subject at 4 weeks [5].

High impact information on PIROXIMONE HYDROCHLORIDE

• Persistent hemodynamic effects without long-term clinical benefits in response to oral piroximone (MDL 19,205) in patients with congestive heart failure [1].
• Three phosphodiesterase (PDE) type III inhibitors were tested and found to inhibit Xenopus oocyte maturation induced by insulin with apparent IC50 values of 2.2 +/- 0.2 microM Cl-930, 25 +/- 3 microM imazodan (Cl-914), and 786 +/- 237 microM piroximone (MDL 19,205) [6].
• The same rank order of potencies was observed for inhibition of insulin-like growth factor-I (IGF-I)-induced oocyte maturation, with IC50 values of 5.5 +/- 0.9 microM Cl-930, 54 +/- 4 microM imazodan, and 1190 +/- 395 microM piroximone [6].
• In four other patients, a single intravenous dose of piroximone (1 mg/kg) resulted in a 35% increase in the first derivative of left ventricular pressure (dP/dt) from 796 to 1,068 mm Hg/s (p less than 0.01) [7].
• Additionally, a further decrease in pulmonary capillary wedge pressure by 13 and 11% (P < 0.05) and in pulmonary vascular resistance by 21 and 19% (P < 0.05) was observed at the piroximone-infusion rates of 5 and 10 micrograms.kg-1.min-1, respectively [8].

Chemical compound and disease context of PIROXIMONE HYDROCHLORIDE

• The hemodynamic and neurohumoral effects of cummulative intravenous doses of piroximone (MDL 19205), a noncatecholamine, nonglycoside, imidazole derivative with positive inotropic and vasodilating properties, were studied in eight patients with severe congestive heart failure [7].
• This study compares the effects of piroximone (MDL 19,205), a new inotropic agent, with dobutamine in dogs with congestive heart failure [9].
• Acute hemodynamic effects of piroximone (MDL 19,205) in patients with moderate congestive heart failure: comparison with sodium nitroprusside [10].
• In patients with cardiomegaly and advanced heart failure given the phosphodiesterase inhibitors enoximone and piroximone we did not observe a rise in MVO2 or the appearance of lactate production in the majority of patients [11].

Biological context of PIROXIMONE HYDROCHLORIDE

• Intravenous (0.5 to 1.0 mg/kg) and oral (0.7 to 4.9 mg/kg) piroximone significantly (p less than 0.05) improved right and left ventricular pump function in both groups while causing an insignificant rise in heart rate and reduction in arterial pressure [12].
• Comparison of the haemodynamic effects of enoximone and piroximone in patients after cardiac surgery [4].
• Maximum aggregation and maximum gradient of platelet aggregation to all stimuli were not changed by either PDE-inhibitor enoximone or piroximone [13].
• Effects of piroximone on the right ventricular function in severe heart failure patients [14].
• 7. Vasodilation could be observed for a longer period and was more pronounced in the enoximone-treated than in the piroximone patients [15].

Anatomical context of PIROXIMONE HYDROCHLORIDE

• By contrast, piroximone and nitroprusside significantly and similarly decreased mean pulmonary artery pressure (MPAP), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP) and pulmonary vascular resistance (PVR), while such changes were not seen following dobutamine [16].
• Moreover, prostacyclin, papaverine, iloprost, and forskolin, compounds which stimulate the enzyme adenylate cyclase, and rolipram (neural specific) and milrinone, enoximone, and piroximone (muscle specific) inhibitors of Type III cAMP PDE and degradation of cAMP, do not inhibit nerve stimulation to most blood vessels [17].
• Studies on the mechanism of the positive inotropic effect of piroximone in cat papillary muscle [18].
• In vitro, piroximone was incubated with dog liver microsomes [19].
• A direct stimulating effect on the myocardium was also demonstrated for enoximone and piroximone by analyzing the systolic pressure versus end-systolic volume ratio [20].

Associations of PIROXIMONE HYDROCHLORIDE with other chemical compounds

• The four drugs to have undergone long-term clinical trials are amrinone, milrinone, enoximone (MDL 17043), and piroximone (MDL 19,025) [21].
• The subsequent 11 patients received 1 mg/kg of piroximone intravenously, and the hemodynamic effects were compared with those of sodium nitroprusside (SN) at a dose-lowering mean blood pressure by 10-20 mm Hg [10].
• Contractile dose-response relationships for amrinone, milrinone, piroximone, and sulmazole were compared in right ventricular papillary muscles isolated from adult and 14-16-day-old immature rabbits [22].
• 5. In vitro, piroximone was metabolized by dog liver microsomes to isonicotinic acid (1) and piroximole (4), with the same ratio as in vivo (1:4 = 0.2) [19].

Gene context of PIROXIMONE HYDROCHLORIDE

• The influence of food on the pharmacokinetics of piroximone (MDL 19.205, CAS 84490-12-0) was evaluated in two groups of 6 healthy male volunteers receiving either 25 or 50 mg of the drug [23].

Analytical, diagnostic and therapeutic context of PIROXIMONE HYDROCHLORIDE

• The increase in stroke work index with a concomitant decrease in left ventricular filling pressure indicates an improvement in systolic performance after treatment with piroximone [24].
• In a subgroup of 10 patients who underwent equilibrium gated radionuclide blood pool scintigraphy before and after intravenous piroximone, end-diastolic volume index tended to increase (106 +/- 42 to 132 +/- 60 ml/m2; p = 0.07), whereas left ventricular filling pressure decreased significantly (26 +/- 8 to 19 +/- 9 mm Hg; p less than 0.01) [24].
• Determination of piroximone in human plasma by high-performance liquid chromatography [25].
• A rapid and selective high-performance liquid chromatographic (HPLC) method using solid-phase extraction (SPE) for measuring piroximone in plasma samples has been developed [25].
• Controlled clinical trials should be undertaken to determine the ultimate efficacy and safety of piroximone in these patients [12].

References