The Influence of Khat on the In-Vitro and In-Vivo Availability of Tetracycline-HCl

The influence of khat on both in-vitro and in-vivo availability of tetracycline-HCl has been evaluated. The in-vitro availability data have reflected a statistically significant interaction between khat extract and tetracycline-HCl in two buffer solutions simulating intestinal and gastric media (phosphate buffer-pH 7 and 0.1 HCl-pH 1.2 respectively). In the in-vivo availability studies, ten adult healthy Yemeni volunteers participated. The obtained in-vivo availability data indicated a statistically significant reduction in most pharmacokinetics parameters. A statistically significant % reduction in the maximum plasma tetracycline-HCl concentration (C_max) and absorption rate constant (K_a) as well as a significant enhancement of time to reach the peak plasma concentration (T_max), were observed as a result of taking tetracycline-HCl just before khat chewing (trial B) and more pronounce during khat chewing (trial D) compared to the control (trial C). In addition a statistically significant % reduction in area under curve (AUC^0→∞) has been observed reflecting a reduction in the extent of in-vivo tetracycline-HCl availability as a result of khat chewing. Statistically significant % reductions in the biologic half-life (t_½) and elimination rate constant (K_el) were also observed.The reduction in tetracycline-HCl concentration when mixed with khat extract, as shown by in-vitro data, may reflect a possible formation of tetracycline-HCl complexes with one or more of khat constituents. The reduction in the rate and extent of in-vivo tetracycline-HCl availability as a result of khat chewing, may be due to the possible formation of non-absorbable tetracycline-HCl complexes with one or more of khat constituents or possible delaying of gastric emptying induced by khat that may prolong the resident time of tetracycline-HCl in the stomach leading to its possible degradation into the less antimicrobial active form epitetracycline.