Research Journal of Pharmaceutical Dosage Forms and Technology. 7(1): January-March, 2015, 01-06 1 ISSN 0975-234X (Print) www.anvpublication.org 0975-4377 (online) RESEARCH ARTICLE The Influence of Khat on the In-vitro and In-vivo availability of Tetracycline-HCl Farah Hamad Farah 1 *, Omer Ali Attef 2 and Abdul-Azim Ahmed Ali 3 1 Department of Pharmaceutics, College of Pharmacy and Health Sciences, Ajman University of Science and Technology, UAE. 2 Department of Pharmaceutical Chemistry, College of Pharmacy and Health Sciences, Ajman University of Science and Technology, UAE 3 Department of Pharmaceutics, College of Pharmacy and Health Sciences, Ajman University of Science and Technology, UAE, *Corresponding Author E-mail: f.hamad@ajman.ac.ae., attef@hotmail.com, ajac.azim@ajman.ac.ae. ABSTRACT: 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. KEYWORDS: availability, pharmacokinetics parameters, tetracycline-HCl, khat. INTRODUCTION: There is no doubt that the habit of khat chewing remains a major problem in Yemeni society and the number of khat chewers seems to be increasing [1,2] . Several reports have been published worldwide revealing the medical effect of khat (Catha edulisForsk.) [1,3,4] , but little is known about the possible interactions between khat constituents and drugs. Address for correspondence: Farah Hamad Farah Department of Pharmaceutics, College of Pharmacy and Health Sciences, Ajman University of Science and Technology, UAE. Received on 21.11.2014 Modified on 15.12.2014 Accepted on 05.01.2015 ©A&V Publications All right reserved Res. J. Pharm. Dosage Form. & Tech. 7(1): Jan.-Mar. 2015; Page 01-06 DOI: The most important khat leaves constituents include more than six alkaloids that are the main determinants of the khat CNS effects, tannins, flavonoids and polyvalent cations, such as calcium, magnesium, iron, cadmium, lead, copper, and zinc [3,4,5,6] .On the other hand antibiotic use in Yemen is high and the statistics of the Ministry of Public Health and Population showed that the antibiotics group was the third group which was imported through the years 2002 and 2003 with percentages of 13.7% and 13.0% respectively from the total number of imported drugs [7,8 ] . Also a study performed in different general public health facilities in Yemen showed that 61% of the prescribed drugs were antibiotics [9] . These findings emphasize the need for conducting research on the influence of khat chewing on the in-vivo availability of antibiotics. A previous study on the effect of