Alteration of the Disposition of Quinine in Healthy Volunteers After Concurrent Ciprofloxacin Administration

作者：Adegbola Adebanjo J; Soyinka Julius O^*; Adeagbo Babatunde A; Igbinoba Sharon I; Nathaniel Thomas I

来源：American Journal of Therapeutics, 2016, 23(2): E398-E404.

DOI：10.1097/MJT.0000000000000087

• pharmacokinetic interaction
• quinine
• ciprofloxacin
• 3-hydroxyquinine

This study evaluated the effects of concurrent ciprofloxacin administration on the disposition of quinine in healthy volunteers. Quinine (600-mg single dose) was administered either alone or with the 11th dose of ciprofloxacin (500 mg every 12 hours for 7 days) to 15 healthy volunteers in a crossover fashion. Blood samples collected at predetermined time intervals were analyzed for quinine and its major metabolite, 3-hydroxquinine, using a validated high-performance liquid chromatographic method. Administration of quinine plus ciprofloxacin resulted in significant increases (P < 0.05) in the total area under the concentration-time curve, maximum plasma concentration (C-max), and terminal elimination half-life (T(1/2)b) of quinine compared with values with quinine dosing alone (AUC: 27.93 +/- 8.04 vs. 41.62 +/- 13.98 h center dot mg/L; C-max: 1.37 +/- 0.24 vs. 1.64 +/- 0.38 mg/L; T(1/2)b: 16.28 +/- 2.66 vs. 21.43 +/- 3.22 hours), whereas the oral plasma clearance markedly decreased (23.17 +/- 6.49 vs. 16.00 +/- 5.27 L/h). In the presence of ciprofloxacin, there was a pronounced decrease in the ratio of AUC (metabolite)/AUC (unchanged drug) and highly significant decreases in C-max and AUC of the metabolite (P < 0.05). Ciprofloxacin may increase the adverse effects of concomitantly administered quinine, which can have serious consequences on the patient. Thus, a downward dosage adjustment of quinine seems to be necessary when concurrently administered with ciprofloxacin.

• 出版日期2016-4