Gastrointestinal blood loss study with a new analgesic compound: nefopam hydrochloride.

A new analgesic compound, neopam HCl, was studied for possible gastrointestinal blood loss liabilities by Cr-51 red cell tagging. It was compared with aspirin in usual therapeutic doses of 1.8 Gm per day. Dosage of nefopam HCl was 180 mg per day (two tablets t.i.d). Twenty healthy male volunteers had fecal blood loss determined after one-week crossover periods of drug investigation, each preceded by one-week no-drug control periods. Results show a significant (P is less than 0.01) increase in occult bleeding in the aspirin-treated subjects from a mean of 0.5 ml to 1.63 ml per 24 hours, the mean increase for the group being 1.13 ml per 24 hours. Nefopam HCl treated subjects had an insignificant change from a control mean of 0.55 ml per 24 hours to 0.60 ml per 24 hours; a third of this group actually had a decrease in measurable blood loss. Reported side effects were minimal in both drug groups.

Spironolactone. II. Bioavailability.

The bioavailability of commercial 25-mg spironolactone tablets and a new tablet preparation containing 100 mg of the drug has been determined in 12 healthy male subjects. After a 200-mg oral dose of the drug given in a solution of polyethylene glycol-400, the peak plasma level of the dethioacetylated metabolite canrenone was 633 +/- 154 ng/ml (mean +/- SD) and was reached at 1.4 +/- 0.43 hr. This peak was higher and was achieved earlier than after either eight 25-mg tablets (480 +/- 155 ng/ml at 2.9 +/- 1.03 hr) or two 100-mg tablets (474 +/- 182 ng/ml at 3.0 +/- 1.37 hr). From the ratio of the 24-hr area under the plasma concentration-time curves, the bioavailabilities of the two tablet preparations relative to the solution were 99.6 +/- 18.2% and 92.1 +/- 22.9%, respectively. The amount of canrenone excreted in the urine by 48 hr was 4.48 +/- 1.26 mg (solution), 6.36 +/- 2.02 mg (eight 25-mg tablets), and 7.81 +/- 1.87 mg (two 100-mg tablets), representing 2% to 4% of the administered dose. It is concluded that urinary excretion of canrenone alone is not a reliable method for determining the bioavailability of spironolactone.