Pharmacokinetics of natural mistletoe lectins after subcutaneous injection.
OBJECTIVE
Knowledge of natural mistletoe lectins (nML) pharmacokinetics can be regarded as essential for further rational studies with mistletoe preparations. Studies with intravenous application of a recombinant type II ribosome inactivating protein (rML) analogous to nML revealed a short half-life of about 13 min in cancer patients. This open-label, phase I, monocenter clinical trial was performed in order to describe the pharmacokinetics of nML.


METHODS
In 15 healthy male volunteers aged 18-42 years, nML were detected with a modified sandwich immuno-polymerase chain reaction (PCR) technique (Imperacer, Chimera Biotec) after single subcutaneous injection of a mistletoe extract (abnobaVISCUM(R) Fraxini 20 mg) with marketing authorization containing about 20 microg nML/ml. Secondary objectives were safety and the number of activated natural killer cells (CD54(+)/CD94(+)).


RESULTS
In none of the volunteers were nML detectable before the injection, and in all volunteers, nML were detected in serum samples after injection. Individual variability, however, was large. Mean and median peak concentrations were reached 1 and 2 h after injection, respectively. In some volunteers, nML were still detectable at the final investigation 2 weeks after injection. The injection resulted in fever and flu-like symptoms in all volunteers, but no serious adverse events occurred. All symptoms and local reactions at the injection site completely disappeared within a range of 4-95 days. The number of activated natural killer (NK) cells did not change.


CONCLUSIONS
Natural ML from abnobaVISCUM Fraxini 20 mg are detectable in serum after a single subcutaneous injection. Detectability is considerably longer compared with intravenously administered rML. The subcutaneous injection of this preparation without usual pretreatment with lower doses results in short-lasting fever and other flu-like symptoms.
Huber
Roman
R
Department of Environmental Health Sciences, University Hospital Freiburg, Breisacher Str. 115b, 79106 Freiburg, Germany. roman.huber@uniklinik-freiburg.de
Eisenbraun
Jürgen
J
Miletzki
Barbara
B
Adler
Michael
M
Scheer
Rainer
R
Klein
Reinhild
R
Gleiter
Christoph H
CH
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D006801:Humans; D007279:Injections, Subcutaneous; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D014784:Mistletoe; D037121:Plant Lectins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D028321:Plant Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D016133:Polymerase Chain Reaction / Q000379:methods
D015415:Biomarkers; D037121:Plant Lectins; D028321:Plant Preparations
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