1 Propyphenazone 220 mg was administered orally to volunteers. Maximum plasma concentrations between 1.5 ,ug/ml and 3.5 Hg/ml were found 30 min later. After comparable doses plasma concentrations in dog and rabbit were lower. The distribution volumes were 2 1/kg. 2 The major metabolic route of propyphenazone is demethylation. The main urinary metabolite is the enolglucuronide of N-(2)-demethylpropyphenazone. 3 Aminopyrine is rapidly and almost completely absorbed after oral administration. Maximum plasma concentrations of 10 .g/ml are reached 1.5 h after a 500 mg dose. The biological half-life is 2-3 h, the relative distribution volume 6007 on average, and binding to plasma proteins approximately 15%. 4 Unchanged aminopyrine is only excreted in small quantities. The major routes of metabolism are demethylation (4-methylaminoantipyrine and 4-aminoantipyrine) and acylation (4-acetyl and 4-formylaminoantipyrine). There are other biotransformation products. 5 After oral administration of [14C]-dipyrone 480 mg the maximum serum concentration of 13.4±0.8 ,ug/ml occurred at 1-1.5 hours. 6 Dipyrone was not detectable in serum or urine. Four of seven metabolites were identified, and were identical with the main metabolites of aminopyrine.

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1 The absorption, excretion, distribution and metabolism of a new antidepressant agent, nomifensine, was examined in rats, dogs and monkevs. After oral administration ot '4C-nomifensine 1 mg/kg body weight, the compound was absorbed rapidly, and as shown in rats and dogs, virtually completely. Nomifensine was predominantly found in a conjugated form in the plasma of rats, dogs and monkeys. Nomifensine was bound to serum proteins (approximately 60%) and the degree of binding was not species specific. 2 The maximum levels of total radioactivity (unchanged drug and metabolites) in the blood were 0.50 + 0.14 gg equiv./ml (n= 5) in dogs and 0.34 + 0.17 jg equiv./ml (n = 6) in monkeys. These leves were markedly higher than those in rats, with values of 0.034 ± 0.014 gg equiv./ml at 0.5-0.75 h and 0.048 + 0.018 jLg equiv./ml at 2-8 h after dosing (second peak; n= 19). 3 The ratio of radioactivity in organs and tissues relative to plasma was small and similar to that in blood. The highest concentrations of radioactivity were measured in the excretory organs; the lowest concentrations were found in the brain. When multiple doses of '4C-nomifensine were administered accumulation was minimal. 4 After single oral doses, the plasma levels of radioactivity were higher than those of blood.Accumulation of unconjugated nomifensine in plasma could not be demonstrated in dog, and multiple doses of the drug had no influence on the elimination of either conjugated or unconjugated nomifensine. 5 Rats excreted about 50%and dogs excreted about 70% of the compound in urine, predominantly as conjugates. The metabolites found in man were also found in monkey, these being 4'-hydroxy nomifensine, 4'-hydroxy-3'-methoxy nomifensine and 3'-hydroxy-4'-methoxy nomifensine.

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