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Enhanced drug metabolism after sulfinpyrazone treatment in patients aged 50 to 60 years

Gesteigerter Arzneimittelmetabolismus bei 50–60jährigen Patienten nach Sulfinpyrazon-Therapie

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Summary

The induction of liver drug metabolism was investigated in five patients before and after the administration of 800 mg sulfinpyrazone daily for 4 weeks, by using antipyrine plasma-pharmacokinetics and by determining urinary excretion of 6-β-OH-cortisol and serum gamma-glutamyl-transpeptidase (GGT) activity. Antipyrine half-life was shortened in all patients from a mean value of 12.3±3.9 h to 7.8±2.0 h and antipyrine clearance was increased from 39.0±16.0 ml/min to 57.6±13.7 ml/min. In contrast the volume of distribution of antipyrine was unaffected; the values being 38.0±8.6 liters and 37.4±5.7 liters, respectively. In all patients the excretion of 6-β-OH-cortisol in the urine went up from 65.0±25.7 µg/24 h to 346.8±193.4 µg/24 h. The ratio 6-β-OH-cortisol/free cortisol changed from 4.1 to 15.8. After 21 days of treatment the GGT increased from 17.4±4.9 units/liter to 32.6±12.5 units/liter The data presented confirm that sulfinpyrazone induces drug metabolism in patients of the older age group. Interactions between sulfinpyrazone and other drugs given simultaneously must be borne in mind.

Zusammenfassung

Sulfinpyrazon (Anturano) wird als Uricosuricum wie als Thrombozytenaggregationshemmer meist gleichzeitig mit anderen Medikamenten verabreicht. Die Kenntnis möglicher Einflüsse auf den Arzneimittelstoffwechsel ist für eine sichere medikamentöse Therapie unerläßlich. Deshalb wurde bei fünf Patienten mit einer Indikation für die Sulfinpyrazon-Therapie der Einfluß einer täglichen Gabe von 800 mg Sulfinpyrazon über 4 Wochen auf den hepatischen Arzneimittelstoffwechsel überprüft.

Als Parameter für eine Steigerung des Arzneimittelmetabolismus war die Antipyrin-Plasma-Halbwertszeit bei allen Patienten verkürzt, im Mittel von 12,3±3,9 auf 7,8±2,0 h und die Antipyrin-Clearance von 39,0±16,0 auf 57,6±13,7 ml/min gesteigert. Erwartungsgemäß konstant blieb das Verteilungsvolumen mit 38,0±8,6 bzw. 37,4±5,71. Die Urin-Ausscheidung von 6-β-OH-Cortisol stieg von 65,0±025,7 auf 346,8±193,4 µg/24 h an und das Verhältnis 6-β-OH-Cortisol/freies Cortisol von 4,1 auf 15,8. Nach dreiwöchiger Behandlung war die GGT von 174,±4,9 auf 32,6±12,5 U/l erhöht.

Die Ergebnisse zeigen, daß eine Behandlung mit Sulfinpyrazon auch bei 50–60jährigen Patienten zu einer Induktion des Arzneimittelstoffwechsels führt. Vor allem bei gleichzeitiger Gabe mit oralen Antikoagulantien sollte dies neben der initialen Verstärkung des Antikoagulantieneffektes berücksichtigt werden.

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Authors and Affiliations

  1. Unit of Clinical Pharmacology, Medical Department, University of Heidelberg, Germany

    E. Walter, Ch. Staiger, J. de Vries & E. Weber

  2. Theresienkrankenhaus, Medical Department, Mannheim

    W. Bitzer, M. Degott & K. Jüngling

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  1. E. Walter
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  2. Ch. Staiger
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  3. J. de Vries
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  4. E. Weber
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  5. W. Bitzer
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  6. M. Degott
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  7. K. Jüngling
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Walter, E., Staiger, C., de Vries, J. et al. Enhanced drug metabolism after sulfinpyrazone treatment in patients aged 50 to 60 years. Klin Wochenschr 60, 1409–1413 (1982). https://doi.org/10.1007/BF01716246

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  • DOI: https://doi.org/10.1007/BF01716246

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