Khat (Catha edulis Forsk) and its effect on anti-malarial chemotherapy

Hamood Eyssa, Fayza (2009) Khat (Catha edulis Forsk) and its effect on anti-malarial chemotherapy. PhD thesis, University of Liverpool.

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Abstract

Millions of Yemenis and East Africans habitually chew daily the fresh leaves and twigs of Catha edulis commonly known as khat; it produces a stimulating amphetamine-like effect. Most people believe that khat leaves relieve fatigue and reduce body temperature; therefore it is a common practice to chew khat during sickness and during treatment. The effect of khat chewing on the bioavailability of certain antibiotics has been studied; the outcome of these studies showed that khat chewing significantly reduced the bioavailability of the antibiotics, however, khat and its effect on anti-malarial drugs has not been studied. The aim of this study was to evaluate the effect of khat on antimalarial chemotherapy and to explore possible pharmacokinetic interactions between chloroquine (CQ) and khat duri!1g co-administration in healthy adult Yemeni volunteers. Furthermore, we wanted to determine the effect of khat on CQ concentration, parasitaemia and parasite clearance in Plasmodium falciparum infected patients. In addition, anti-malarial activity was tested in vitro against CQ sensitive-resistant strains. In a two-phase cross-over study, 15 healthy adult male volunteers were given a single dose of 600 mg of CQ with and without khat. Plasma concentrations ofCQ were determined during a 24 h period following drug administration on both occasions. CQ plasma concentrations were determined by a validated HPLC-UV method. Pharmacokinetic parameters ofCQ were calculated using compartmental analysis. In the two periods of treatment, the mean (SD) peak plasma concentrations (Cmax) were 415 (103) nglml (CQ with khat) and 508 (106) ng/ml (CQ alone). The total areas under the curve (ACUO-24) were 2108 (682) ng/h/ml (CQ with khat) and 2797 (845) ng/h Iml (CQ alone). The time taken to reach Cmax (Tmax) was 3.8 (0.41) hand 3.6 (0.51) h. and elimination half-life (tv,) was 7.7 (2.10) hand 7.5 (2.77) h respectively. Statistically significant differences were observed for both (Cmax) (p < .001) and (ACUO-24) (p< .003) of CQ when comparing values with or without khat. These results demonstrat~ a pharmacokinetic interaction between CQ and khat and suggest that the observed interaction may be clinically significant, although the CQ levels were above the therapeutic level for P.falciparum.

Item Type:	Thesis (PhD)
Depositing User:	Symplectic Admin
Date Deposited:	20 Oct 2023 09:24
Last Modified:	20 Oct 2023 09:40
DOI:	10.17638/03174462
Copyright Statement:	Copyright © and Moral Rights for this thesis and any accompanying data (where applicable) are retained by the author and/or other copyright owners. A copy can be downloaded for personal non-commercial research or study, without prior permission or charge
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3174462