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European Journal of Clinical Pharmacology

, Volume 32, Issue 6, pp 607–610 | Cite as

Disposition of moracizine (ethmozine) in healthy subjects after oral administration of radiolabelled drug

  • D. L. Howrie
  • H. J. PieniaszekJr.
  • R. N. Fogoros
  • R. P. Juhl
  • W. L. Schary
  • C. C. WhitneyJr.
  • L. W. Dittert
Originals

Summary

Moracizine (ethmozine) is a phenothiazine derivative with demonstrated antiarrhythmic activity. To characterize the pharmacokinetics and material balance relationships in humans, we have given14C-moracizine·HCl as a single oral dose of 500 mg (50 μCi) to six healthy men. Plasma, urine, and faecal samples were collected for 7 days after administration and the concentrations of total radioactivity and intact moracizine were determined by liquid scintillation counting and HPLC, respectively.

Urine and faecal recovery accounted for 95% of the administered radioactivity. Most of this radioactivity was found in the faeces (59%). Only 0.05% of the dose was recovered from urine as intact moracizine.

The Cmax and AUC for moracizine equivalents of total radioactivity were 4- and 18-fold higher, respectively, than the corresponding values for intact moracizine. Additionally, both the disappearance of total radioactivity from plasma and its excretion rate into urine were slower in comparison to intact drug. Terminal t1/2 values calculated from plasma concentration-time data were 85.2 and 3.5 h for total radioactivity and intact moracizine, respectively. However, based on urinary excretion rates, the t1/2 for total radioactivity was shorter (29.3 h) while the t1/2 for intact drug was comparable (2.7 h) to the results obtained from the plasma data. The oral plasma clearance of moracizine was relatively large (2.2l·min−1), suggesting first-pass metabolism. The estimated oral systemic availability of moracizine was 34%.

Key words

moracizine·HCl antiarrhythmic ethmozine radiolabelled pharmacokinetics material balance healthy subjects 

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Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • D. L. Howrie
    • 1
  • H. J. PieniaszekJr.
    • 1
  • R. N. Fogoros
    • 2
  • R. P. Juhl
    • 1
  • W. L. Schary
    • 4
  • C. C. WhitneyJr.
    • 3
  • L. W. Dittert
    • 1
  1. 1.School of PharmacyUniversity of PittsburghPittsburghUSA
  2. 2.School of MedicineUniversity of PittsburghPittsburghUSA
  3. 3.DuPont Pharmaceuticals Medical Products Department Drug Metabolism SectionStine-Haskell Research CenterNewarkUSA
  4. 4.Medical Research SectionDuPont PharmaceuticalsWilmingtonUSA

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