Summary
Intraindividual variations of 8-methoxypsoralen (8-MOP) plasma levels were investigated. On at least 3 consecutive days of treatment 8-MOP levels were determined 2 h following the administration of 0.56–0.82 mg/kg b.w. On day 1 a complete plasma level-time profile was obtained. Interindividually, 8-MOP plasma levels varied from 0–654 ng/ml. Intraindividual variation was considerably less being 1.2–5.3-fold. In one patient who showed a lower absorption rate of 8-MOP plasma levels varied from 0–126 ng/ml. There was a rather close correlation (r=0.81) of the variation of 8-MOP plasma levels (determined as the ratio of highest to lowest plasma level) and mean plasma level, intraindividual variation decreasing exponentially with increasing 8-MOP plasma levels. Parameters determining variation of 8-MOP plasma levels are the intrinsic hepatic clearance, liver blood flow, and possibly the absorption of the drug from gastrointestinal tract. To keep intraindividual variation as low as possible ingestion of the drug together with a standardized meal is suggested. Drugs interfering with hepatic metabolism or liver blood flow should be avoided.
Zusammenfassung
Intraindividuelle Schwankungen der 8-Methoxypsoralen-(8-MOP)-Plasmaspiegel wurden untersucht. 8-MOP-Plasmaspiegel wurden 2 h nach oraler Gabe von 0,56–0,82 mg/kg Körpergewicht an mindestens 3 aufeinander folgenden Behandlungstagen bestimmt. Am 1. Untersuchungstag wurde ein vollständiger Plasmaspiegel-Zeit-Verlauf gemessen. Die interindividuellen Schwankungen der 8-MOP-Plasmaspiegel betrugen 0–654 ng/ml. Die intraindividuellen Schwankungen waren wesentlich geringer (1,2–5,3fach). Bei einem Patienten, der eine niedrigere Resorptionsgeschwindigkeit für 8-MOP aufwies, schwankten die Plasmaspiegel zwischen 0 und 126 ng/ml. Die intraindividuellen Schwankungen (bestimmt als Quotient aus höchstem zu niedrigstem Plasmaspiegel) waren relativ eng mit dem Plasmaspiegelmittelwert korreliert (r=0,81). Die intraindividuellen Schwankungen nehmen mit ansteigendem 8-MOP-Plasmaspiegel exponentiell ab. Die Schwankungen der 8-MOP-Plasmaspiegel werden durch die intrinsische hepatische Clearance, die Leberdurchblutung und möglicherweise auch durch unterschiede in der Resorption aus dem Gastrointestinaltrakt bestimmt. Um die intraindividuellen Schwankungen der 8-MOP-Plasmaspiegel möglichst niedrig zu halten, wird empfohlen, das Arzneimittel zusammen mit einer standardisierten Mahlzeit zu verabreichen. Ferner sollte die Gabe von Pharmaka, die mit der Metabolisierung in der Leber oder mit der Leberdurchblutung interferieren, möglichst vermieden werden.
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Dedicated to Prof. E. Mutschler, PhD, MD, on behalf of his 50th birthday
The present investigation was partly supported by the Doktor-Robert-Pfleger-Stiftung
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Schäfer-Korting, M., Korting, H.C. Intraindividual variations of 8-methoxypsoralen plasma levels. Arch Dermatol Res 272, 1–7 (1981). https://doi.org/10.1007/BF00510387
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DOI: https://doi.org/10.1007/BF00510387