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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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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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Cmax :

maximum plasma concentration

Cmax,norm :

dose and body weight normalized; Cmax


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

tmax :

time of the maximum plasma concentration


area under the curve from t=0 to infinity


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


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


area under the curve extrapolated from tn to infinity

AUCnorm :

dose and body weight normalized AUC-values

t1/Z :

terminal half-life


amount excreted into urine


renal clearance


  1. Asamoto H, Kawakami A, Ozawa Y, Fujii H, Iso S, Kotake T, Horiuchi Y, Shinohara H, Sekiyama T (1989) Theophylline clearance in patients with asthma during concomitant administration of MY 5116 (repirinast). Ther Res 10: 4011–4014

  2. Dunnett CW (1964) New tables for multiple comparisons with a control. Biometrics 20: 482–491

  3. Ekado G, Kami Y, Okada Y, Katami Y, Takaichi M, Ohtsuki T, Yokojima T, Uchide M, Morinaka Y (1986) Study of the pharmacokinetics of MY-5116 — 2. Metabolism and species differences. Clin Rep 20: 941–955

  4. Esumi Y, Jin Y, Uohama K, Kashiwazaki K, Yohoshima, T (1986) Studies on pharmacokinetics of MY-5116 — 1. Absorption, distribution and excretion in rats. Clin Rep 20: 925–940

  5. Gibaldi M, Perrier D (1982) Pharmacokinetics 2nd edition. Dekker, New York

  6. Hauschke D, Steinijans VW, Diletti E (1990) A distribution-free procedure for the statistical analysis of bioequivalence studies. Int J Clin Pharmacol Ther Toxicol 28: 72–78

  7. Iwamoto A, Ichide M, Takamatsu Y, Kondo H, Onuma K (1986) Studies on pharmacokinetics of MY-5116 — 3. Absorption, excretion and metabolism in man. Clin Rep 20: 956–964

  8. Miyamoto A, Takahaski S, Shida T, Kabe J, Makino S (1986) Clinical evaluation of a new anti-allergic agent, MY-5116, for adult bronchial asthma. Med Consult New Remed 23: 251–276

  9. Pabst G, Jaeger H (1990) Review of methods and criteria for the evaluation of bioequivalence studies. Eur J Clin Pharmacol 38: 5–10

  10. Schaefer HG, Beermann D, Horstmann R, Wargenau M, Heibel B (1990) The effect of food on the pharmacokinetics of the active metabolite of repirinast. 5th annual meeting of the American Association of Pharmaceutical Scientists (AAPS), Las Vegas, USA, 4–8 Nov. 1990, Pharm Res 7: S245

  11. SAS Institute Inc., SAS Circle Box 8000, Cary, NC 27512-8000 U.S.A.

  12. Takagi K, Kuzuya T, Horiuchi T, Nadai M, Apichartpichean R, Ogura Y, Hasegawa T (1989) Lack of effect of repirinast on the pharmacokinetics of theophylline in asthmatic patients. Eur J Clin Pharmacol 37: 301–303

  13. Takahashi K, Shono T (1986) Effects of MY-5116 on PCA reaction and on histamine release from peritoneal cells induced by antigen antibody reactions. Folia Pharmacol Jap 87: 29–39

  14. Takahashi K, Arai Y, Kadowaki S, Shono T, Yuki S (1986) General pharmacology of a new anti-allergic drug, isoamyl 5,6-dihydro 7,8-dimethyl-4,5-dioxo-4H-pyrano (3,2c) quinoline-2-carboxylate (MY-5116) and its main active metabolite. Pharmacometrics(Oyo Yakuri) 32: 233–249

  15. Takishima T, Mue S, Ohmi T, Takasugi R, Takahashi K (1986) Clinical trial of an antiallergic drug MY-5116 for bronchial asthma. Japan J Clin Exp Med 63: 2723–2733

  16. Yamada N, Suzuki K, Kadowaki S, Tabahashi K, Mizogami S (1988) Mechanism of action of MY-1250 a main metabolite of repirinast (MY-5116) in inhibiting histamine release from rat mast cells: Phosphorylation of 78K-Dalton protein. Japan J Pharmacol 46 [Suppl]: 62 P Abstract O-49

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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