Summary
The kinetics of single 30-mg oral doses of oxazepam were determined in 22 male and nine female volunteers aged 20–86 years. Oxazepam plasma concentrations were measured in multiple plasma samples drawn during 36 h after each dose. Mean kinetic variables in males and females, respectively, were: elimination half-life, 7.5 and 8.5 h; volume of distribution, 0.96 and 1.17 l/kg; clearance, 1.48 and 1.70 ml/min/kg. Sex differences were not significant, nor were any of the kinetic variables significantly related to age. However, oxazepam clerance increased significantly with heavier cigarette smoking (r=0.48,p<0.01). Mean clearance in smokers (1.98 ml/min/kg) was significantly higher than in non-smokers (1.23 ml/min/kg,p<0.01). Thus, smoking is a more important determinant of oxazepam clearance than age or sex.
Zusammenfassung
Bei 31 Versuchspersonen (22 männliche, neun weibliche) wurde die Kinetik von Oxazepam nach einer einmaligen oralen Gabe von 30 mg gaschromatographisch bestimmt. Das mittlere Alter der beiden Versuchsgruppen lag bei 51 bzw. 44 Jahren (Bereich: 22–86 Jahre). Die kinetischen Variablen für die männlichen und weiblichen Versuchsgruppen lauten (in Klammern der Bereich): Eliminationshalbwertzeit: 7,5 h (3,2 h–19,8 h) bzw. 8,5 h (3,4 h–12,4 h); Verteilungsvolumen: 0,96 (0,44–2,91) bzw. 1,17 (0.60–-3,12) l/kg Körpergewicht; Clearance 1,48 (0,62–3,00) bzw. 1,70 (0,56–3,73) ml/min/kg; Zeitpunkt der maximalen Plasmakonzentration: 2,2 h (0,75 h–6,0 h) bzw. 1,7 h (0,75 h–3,0 h) nach Tabletteneinnahme; maximale Plasmakonzentration 646 (242–1195) bzw. 653 (447–854) ng/ml.
Geschlechtsbedingte Unterschiede in der Kinetik ließen sich im Gegensatz zu anderen Benzodiazepinen, wie z.B. Diazepam oder Desmethyldiazepam, nicht nachweisen. Ebenso bestanden keine signifikanten Korrelationen zwischen den kinetischen Variablen und dem Alter der Probanden. Auch hierin unterscheidet sich Oxazepam von den meisten anderen Benzodiazepinen. Dagegen ließ sich eine signifikante Beziehung zwischen der Clearance und dem Zigarettenkonsum der Probanden ableiten: sie war bei den Rauchern mit 1,98 ml/min/kg deutlich höher als bei den Nichtrauchern (1,23 ml/min/kg) (p<0,01).
Im Gegensatz zu anderen Benzodiazepinen beeinflussen die Rauchergewohnheiten die Kinetik des Oxazepam mehr als die alters- oder geschlechtsgebundenen Faktoren.
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Supported in part by Grant Oc 10/4 from the Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg, Federal Republic of Germany; and Grant MH-34223 from the United States Public Health Service
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Ochs, H.R., Greenblatt, D.J. & Otten, H. Disposition of oxazepam in relation to age, sex, and cigarette smoking. Klin Wochenschr 59, 899–903 (1981). https://doi.org/10.1007/BF01721923
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DOI: https://doi.org/10.1007/BF01721923