Pharmacokinetics of cathinone, cathine and norephedrine after the chewing of khat leaves

Abstract

AimThe stimulating herbal drug khat is habitually used in East Africa and the Arabian peninsula but is also imported into other countries. The aim was to study the pharmacokinetics of its alkaloids cathinone, cathine and norephedrine. Methods Four volunteers chewed khat leaves in an amount equivalent to onequarter of that used in a typical khat session. Blood samples were collected up to 80 h and the alkaloids were assayed using gas chromatography-mass spectrometry. The data were evaluated using computerized pharmacokinetic compartmental analysis. Results The plasma concentration-time data for the alkaloids could be described using a two-compartment model with two-segment absorption. The mucosa of the oral cavity is considered to be the first absorption segment, where the major proportion of the alkaloids is absorbed (mean ± SD 59 ± 21% for cathinone and 84 ± 6% for cathine). The extraction of the alkaloids from the leaves by chewing was very effective with only 9.1 ± 4.2% remaining as a residue. Cathinone was eliminated from the central compartment with a mean half-life of 1.5 ± 0.8 h. The half-life of cathine was 5.2 ± 3.4 h. The metabolism of cathinone to norephedrine had a substantial influence on its plasma concentration profile. Psychophysical functions were essentially unaffected by the chewing of khat. Conclusions The pharmacokinetics of khat alkaloids in humans explain why chewing is the preferred form of khat ingestion. Subjects absorbed a mean dose of 45 mg of cathinone, and did not suffer any severe adverse reactions.

Khat (Catha edulis)-induced apoptosis is inhibited by antagonists of caspase-1 and -8 in human leukaemia cells

“…The alkaloid fraction of khat is very efficiently extracted by chewing, and the major compounds are absorbed in the oral cavity (Toennes et al, 2003). Despite the body of knowledge on the adverse systemic effects of khat related to neurological disorders, hypertension, myocardial infarction and development of cancer (Al-Motarreb et al, 2002 for a recent review), so far, very little is known about the biological effects of khat on cells (Carvalho, 2003).…”

La toxicité du khat impose-t-elle une modification de la réglementation de son usage en Europe?

“…Les concentrations en alcaloïdes sont variables (pour 100 grammes de feuilles fraîches) : 36 à 114 mg de cathinone, 83 à 120 mg de cathine, et 8 à 47 mg de noréphé-drine [10,18,19]. Al Motarreb et coll.…”

“…La consommation usuelle varie de 100 à 500 grammes, lentement mâchées pendant 2 à 10 heures [15,22]. Le jus issu de la mastication est avalé alors que les résidus ne le sont pas [18]. Cette pratique assure une très bonne extraction des alcaloïdes : environ 10 % à 20 % restant dans le résidu de feuilles [8].…”

“…L'absorption des constituants a lieu apparemment en deux phases : la première via la muqueuse buccale, la seconde par déglutition du jus [18]. Lors de la mastication, l'absorption est lente, majoritairement digestive et dans une moindre mesure sublinguale.…”

“…Seulement 7 % ou moins de la dose internalisée de cathinone sont retrouvés inchangés dans l'urine [15,18]. Le métabolisme consiste en une réduction sté-réospécifique en kéto.…”