Pharmacokinetics and immunomodulatory effects of phytotherapeutic lozenges (bonbons) with Echinacea purpurea extract.
The relative bioavailability of the major alkamides, dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides, from Echinacea purpurea phytotherapeutic lozenges at three different dose levels (0.07, 0.21 and 0.9 mg) was evaluated in a pharmacokinetic study in humans and the possible effects on the immunological system were measured. Alkamides were found to be rapidly absorbed and measurable in plasma 10 min after administration of 0.21 and 0.9 mg lozenges and remained detectable for 3h for the 0.21 mg lozenges and for more then 3h for the 0.9 mg lozenges; 0.07 mg lozenges were measurable 20 min after administration and remained detectable for only 2h after the administration. A significant dose-independent down-regulation of the pro-inflammatory cytokines IL-12p70, IL-8, IL-6, IL-10 and TNF was observed 24h after oral administration. The results of non-compartmental pharmacokinetic analysis revealed that a C(max) of (0.65+/-0.41 ng/ml) was reached at 32 min with the 0.07 mg lozenges, (1.00+/-0.21ng/ml) at 25 min with the 0.21 mg lozenges and (8.88+/-5.89 ng/ml) at 19 with the 0.9mg lozenges. As evidenced by the dose-exposure relationship, no significant departure from dose proportionality was observed, indicating linearity in pharmacokinetics. To get a further insight in pharmacokinetics of dodeca-2E,4E,8Z,10E/Z-tetraenoic isobutylamides a compartmental population pharmacokinetic model was developed applying mixed effect modelling procedure. The results demonstrate that within the dose range studied pharmacokinetics of dodeca-2E,4E,8Z,10E/Z-tetraenoic isobutylamides are linear and that absorption is very rapid (t(1/2)=6 min) with apparently no lag time, thus indicating the possibility that a fraction of the drug is absorbed through the oral mucosa.
Guiotto
P
P
Department of Pharmaceutical Sciences, University of Trieste, P.le Europa 1, I-34127 Trieste, Italy.
Woelkart
K
K
Grabnar
I
I
Voinovich
D
D
Perissutti
B
B
Invernizzi
S
S
Granzotto
M
M
Bauer
R
R
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D019540:Area Under Curve; D016207:Cytokines / Q000097:blood; D004304:Dosage Forms; D004305:Dose-Response Relationship, Drug; D020900:Echinacea / Q000737:chemistry*; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D016207:Cytokines; D004304:Dosage Forms; D005231:Fatty Acids, Unsaturated; D010936:Plant Extracts; D053284:Polyunsaturated Alkamides; C501801:dodeca-2Z,4E,10Z-trien-8-ynoic acid isobutylamide