Pharmacokinetics and pharmacodynamics of p-hydroxylamino-propiophenone

p-Hydroxylaminopropiophen-one (PHAPP), the metabolite of p-amino-propiophenone. is a direct methemoglobin former. PHAPP phosphoresces strongly in alcohol with excitation at 330 nm. emission at 450 nm and with a lifetime of 0.8 s. Following im PHAPP 10 mg/kg to mice and rabbits. the blood drug concentration were determined by phosphorimetric method, and the pharmacokinetic parameters were calculated. PHAPP is a oneompartment drug and the blood drug concentration may be calculated by the following equations, CUg/ ml = 47.3exp(-O.0275t)-44.3exp(-0.192t) (for mice);CUg/ml=112.8exp(-0.012t)-38.6exp(-0.270t)(for rabbits). The blood drug level declined rapidly in mice with a t1/2 of 25 min, but decreased slowly with a t1/2 of 63 min in rabbits. The pharmacodynamics of PHAPP were measured as the rate of MetHb formation (%), after im PHAPP 10 mg/kg to rabbits or mice. The MetHb, in mice, was formed rapidly and reached the peak conceritration within l min. and then dropped steeply with a t1/2 of 5.8 min. On the contrary. the MetHb in rabbits decreased slowly with a t1/2 of 66 min. The hysteresis of MetHb formation in rabbits (i.e., the peak concentration time of MetHb formation was later than that of peak drug concentration) was observed. Before and after the peak drug concentration, the MetHb (%) may be calculated from drug concentration by equation I and II, respectively. I In (MetHb %)=3.17+1.03 In C; II In (MetHb %)=3.61+1.31 In C. The dose reduction factor (DRF) of PHAPP against NaCN poisoning in mice was 2.0. which is similar to that of dimethylaminopheno] (DRF = 1.8).