Pharmacokinetic Interactions between quinine and ciprofloxacin in health volunteers
This study determined the baseline pharmacokinetic parameters of quinine and its major metabolite (3-hydroxyquinine) and evaluated the effect of concurrent administration of ciprofloxacin on the pharmacokinetic parameters of quinine in healthy volunteers with a view of obtaining information that will guide the usage of quinine when co-administered with ciprofloxacin. Ethical approval was obtained from the Ethics Committee of the Institute of Public Health, Obafemi Awolowo University, Ile Ife and written informed consent was obtained from the healthy volunteers. Each subject was assessed at screening to be healthy by physical examination, medical history and routine laboratory evaluations. The study was implemented as a 2-period design. In period 1, a single oral dose (600 mg) of quinine sulphate was given to each of twelve volunteers and blood samples were withdrawn at pre-determined intervals over 48 hours. After a wash out period of 1 month, each volunteer received multiple oral doses of 500 mg ciprofloxacin tablet every 12 hours for 7 days and a single oral dose of 600 mg quinine sulphate was then given concurrently with the 11th dose of ciprofloxacin, and blood samples were taken at predetermined intervals again over 48 hours after drug administration. The blood samples were centrifuged to obtain plasma which was stored in the freezer at -20 °C until the samples were analysed for plasma levels of quinine and its main metabolite, 3-hydroxyquinine, by High Performance Liquid Chromatographic method. The pharmacokinetic parameters of quinine with or without ciprofloxacin were determined and the differences between the two pairs of data were evaluated by the Student’s t-test. A p-value of < 0.05 was considered statistically significant. Concurrent administration of quinine and ciprofloxacin resulted in significant (p < 0.05) increased elimination half life (t1/2), maximum plasma concentration (Cmax) and area under the curve (AUC0-∞) of quinine by 32 %, 19 % and 49 % respectively. Similarly, ciprofloxacin caused a marked decrease of 31 % in the plasma clearance (Clp) of quinine. The Cmax and AUC0-∞ of 3-hydroxyquinine were also significantly reduced when ciprofloxacin was co-administered with quinine by 53 % and 44 % respectively. In addition, the metabolic ratio of quinine was markedly decreased by 63 % when co-administered with ciprofloxacin. These results showed that the formation of 3-hydroxyquinine had been hindered in the presence of ciprofloxacin. This might be attributed to the inhibition of an enzyme, CYP 3A4, which is responsible for the conversion of quinine to 3-hydroxyquinine. The study concluded that there is a modest and significant pharmacokinetic (metabolic) interaction between quinine and ciprofloxacin in vivo when co-administered.