[Affinity of T-3761 to ocular melanin and intraocular dynamics].

The affinity of T-3761 to melanin was examined with synthetic melanin comparing other quinolones. The binding rates with synthetic melanin were from 37% to 48% for tosufloxacin, sparfloxacin, ciprofloxacin and norfloxacin. Binding rate of ofloxacin at 28% was lower and T-3761 was lowest at 22%. Intraocular dynamics of T-3761 and ofloxacin were investigated in pigmented rabbits after a single oral administration at a dose of 20 mg/kg. In both drugs, the concentrations in the melanin bearing tissues were higher and the disappearances from the melanin bearing tissues were more slowly than those of the non-melanin bearing tissues. T-3761 concentrations in the melanin bearing tissues were significantly lower than ofloxacin. In vitro uptake amount to melanin bearing tissue of ofloxacin was 1.4-2.4 times larger than that of T-3761.

[Placental transfer and mammary excretion of [14C] T-3761 in rats and mice].

Placental transfer and mammary excretion of radioactivity were investigated in the pregnant rats on day 19 of pregnancy, in the pregnant mice on day 18 of pregnancy, and in the lactating rats after oral administration of 5 mg/kg of [14C] T-3761. 1. Transfer of radioactivity to fetus was observed in rats and mice and the concentration in fetus was 0.2-0.5 times higher than the maternal plasma. 2. The radioactivity was excreted into the milk and the concentration in milk was higher than those of blood levels (milk/blood = 1.3-5.8). The radioactivity in milk declined more slowly than in blood.

The formation of metabolites of mephentermine by microsomal and cytosolic preparations of male Wistar rat livers.

1. Metabolites of mephentermine (MP), phentermine (Ph), p-hydroxy-MP, p-hydroxy-Ph, N-hydroxy-MP and N-hydroxy-Ph on incubation with rat liver microsomal and cytosolic preparations were identified by g.l.c. and g.l.c.-mass spectrometry. 2. Identification of the metabolites indicated the following new metabolic routes of MP: NADPH-dependent microsomal formation of p-hydroxy-MP from MP, of p-hydroxy-Ph from p-hydroxy-MP, and the NADH-dependent microsomal formation of Ph from N-hydroxy-Ph.

Metabolism of mephentermine in male guinea pigs and male mice.

1. Urinary metabolites of mephentermine (MP), after i.p. administration of MP to male Hartley guinea pigs and mice, were identified by g.l.c.-electron impact (EI) mass spectrometry. Excretion of urinary radioactivity, and metabolites of 3H-MP, after i.p. administration, were determined by preparative t.l.c.-liquid scintillation counting. 2. About 27% of the radioactivity administered was excreted in the 24 h urine of guinea pigs, and 36% dose was excreted in 5 days. In mice, about 47% of the radioactivity was excreted in the 24 h urine, and 52% in 5 days. 3. Excretion rates of metabolites detected in the 24 h urine of guinea pigs were phentermine (Ph, 7.8%), a conjugate of N-hydroxyphentermine (N-hydroxy-Ph, 3.6%), p-hydroxyphentermine (p-hydroxy-Ph, 1.0%) and its conjugate (2.9%), and other metabolites (conjugates of MP and Ph, N-hydroxymephentermine (N-hydroxy-MP) and its conjugate, p-hydroxymephentermine (p-hydroxy-MP) and its conjugate, and N-hydroxy-Ph; less than 1.0%). The rates of excretion for mice were Ph (11.7%), conjugates of p-hydroxy-MP (3.1%), Ph (2.7%) and p-hydroxy-Ph (1.6%), and N-hydroxy-Ph (1.2%) and other metabolites (conjugates of MP and N-hydroxy-Ph, N-hydroxy-MP and its conjugate, p-hydroxy-Ph, and p-hydroxy-MP; less than 1.0%). 4. These results indicate that MP administered to mice is metabolized mainly to Ph and p-hydroxy-MP by N-demethylation and p-hydroxylation of the parent compound, and in guinea pigs the primary metabolic reaction of MP is N-demethylation producing Ph.(ABSTRACT TRUNCATED AT 250 WORDS)