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Pharmacokinetics of the active metabolite of the prodrug repirinast in healthy Caucasian volunteers after a single oral dose

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Summary

The pharmacokinetics of BAY w 8199, the active metabolite of the prodrug repirinast (BAY u 2372), has been investigated after oral administration of 150, 300 and 450 mg repirinast to twelve healthy male Caucasians.

Plasma BAY w 8199 concentrations were very variable between subjects. The mean peak level (geom. mean; 1s-range) was 0.14 (0.08–0.25), 0.19 (0.13–0.29) and 0.24 (0.14–0.42) mg/l after the 150, 300 and 450 mg doses, respectively. Peak levels were reached 0.5–2.5 h after drug intake. Terminal half-lives were calculated as 5.9 h (150 mg), 8.0 h (300 mg) and 9.8 h (450 mg).

The dose proportionality of the plasma profiles of BAY w 8199 and of its excretion in urine was demonstrated by testing several parameters.

About 7.4% of each dose (calculated as BAY w 8199) was excreted in urine over 36 h. The renal clearance of about 27 l/h suggests that BAY w 8199 is excreted by tubular secretion in addition to glomerular filtration.

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Abbreviations

Cmax :

maximum plasma concentration

Cmax,norm :

dose and body weight normalized; Cmax

C'(n):

concentration calculated for time tn from a log-linear regression line

tmax :

time of the maximum plasma concentration

AUC:

area under the curve from t=0 to infinity

AUC(0–12):

area under the curve from t=0 to t=12 hours

AUC(0–tn):

area under the curve from t=0 to the last data point

AUC(tn–∞):

area under the curve extrapolated from tn to infinity

AUCnorm :

dose and body weight normalized AUC-values

t1/Z :

terminal half-life

Ae:

amount excreted into urine

CLR :

renal clearance

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Beermann, D., Schaefer, H.G., Wargenau, M. et al. Pharmacokinetics of the active metabolite of the prodrug repirinast in healthy Caucasian volunteers after a single oral dose. Eur J Clin Pharmacol 42, 307–312 (1992). https://doi.org/10.1007/BF00266353

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Key words

  • Pharmacokinetics
  • Caucasians
  • Repirinast
  • Antiallergic drug
  • single dose
  • oral administration
  • metabolite
  • BAY w 8199