title: Alteration of the Disposition of Quinine in Healthy Volunteers After Concurrent Ciprofloxacin Administration.
abstract: 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 (Cmax), and terminal elimination half-life (T1/2b) of quinine compared with values with quinine dosing alone (AUC: 27.93 ± 8.04 vs. 41.62 ± 13.98 h·mg/L; Cmax: 1.37 ± 0.24 vs. 1.64 ± 0.38 mg/L; T1/2b: 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 Cmax 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.
authors.affiliation: Departments of 1Pharmaceutical Chemistry and 2Clinical Pharmacy and Pharmacy Administration, Obafemi Awolowo University, Ile-Ife, Nigeria; and 3Department of Biomedical Sciences, University of South Carolina School of Medicine Greenville, Greenville, SC.
authors.forename: Adebanjo J
authors.initials: AJ
authors.lastname: Adegbola
authors.forename: Julius O
authors.initials: JO
authors.lastname: Soyinka
authors.forename: Babatunde A
authors.initials: BA
authors.lastname: Adeagbo
authors.forename: Sharon I
authors.initials: SI
authors.lastname: Igbinoba
authors.forename: Thomas I
authors.initials: TI
authors.lastname: Nathaniel
mesh_terms: D000328:Adult; D019540:Area Under Curve; D002939:Ciprofloxacin / Q000494:pharmacology*; D018592:Cross-Over Studies; D065692:Cytochrome P-450 CYP3A Inhibitors / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D011802:Quinidine / Q000031:analogs & derivatives / Q000097:blood; D011803:Quinine / Q000378:metabolism*
chemical_list: D065692:Cytochrome P-450 CYP3A Inhibitors; C013569:3-hydroxyquinidine; D002939:Ciprofloxacin; D011803:Quinine; D011802:Quinidine