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

Aim  The 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 one-quarter 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.