>   >   >   >  1994 Vol.22 no.7 (133-179)
Issue Vol.22 no.7 (133-179)
Title Phase I study of a new antianxiety drug,SC-48274
Author A.Takahashi et al.

 A phase I study of a piperidinedione derivative, SC-48274 was conducted in 17 healthy subjects who gave informed consent at a Clinical Pharmacology ward of Kitasato Univ. Seven subjects were enrolled in each step of a single dose and repeated dose study. SC-48274 was given to five subjects, while a placebo was given to two subjects in a single blind manner in every step. In the single rising dose study, doses were increased from 50 mg at step I to 400 mg at step V. Alternation of pharmacokinetic parameters by food intake was evaluated at step IV. In repeated dose study SC-48274 was administrated continuously for 7 days as 200 mg twice a day. 1) Clinical pharmacological effects. Sleepiness, light-headness and headaches appeared at every step. There was no differenee between SC-48274 and placebo in the incidence and degree of severity in each symptom. The highest dose of 400 mg SC-48274 as well as all other doses, was tolerated, hence, the maximum tolerated dose was not determined. 2) Effects on physical and laboratory tests.

(1) No significant abnormal findings were noted in respect to blood pressure, pulse rate, body temperature, urinalysis, hematological parameters or endocrinological tests (prolactin, cortisol, T3, T4).

(2) Psychological working tests. No significant influence was noted in psychological working tests such as Uchida-Kraepelin test, memory drum, delayed matching task, reaction time, flicker fusion test, tapping test.

(3) Equilibrium tests. No significant influence was noted in gravimetric test. In eye tracking test, two subjects receiving SC-48274 showed alteration from normal to a slightly saccadic pattern.

(4) EEG. No significant influence was noted in EEG.

(5) ECG. In ECG, the subjects receiving SC-48274 displayed prolongation of PR and QRS ar the high dose.

(6) Blood biochemical parameters. Elevation of hepatic transiminase (GOT, GPT gamma-GTP) was observed in one subject receiving SC-48274 in the repeated dose study. There was a decrease in serum iron in both the SC-48274 and placebo. 3) Clinical pharmacokinetics. Serum concentration of SC-48274 reached its maximum at 1.1-1.4 hr after oral administration and thereafter it gradully decreased to give a mean half-life of 6.9 hr. The average C(max) of SC-48274 in step 1, 2, 3, 5 were 0.28, 0.54, 1.28 and 2.54 microg/ml, respectively, with the increase almost proportional to the dose level. Decrease of C(max) and AUC and prolongation of T(max) were observed in step IV. These alterations of pharmacokinetic parameters were due to postprandial administration. In the repeated dose study, the steady state was supposedly reached on days 2similar3 of administration.