title: Cations in the didanosine tablet reduce ciprofloxacin bioavailability.
abstract: The effect of the magnesium-aluminum cations contained in didanosine chewable tablets on ciprofloxacin pharmacokinetics was evaluated in 12 healthy volunteers. The study was designed as a randomized, balanced, open, two-period, two-treatment crossover trial with a 7-day washout period between treatments. In one phase, subjects received a single 750 mg ciprofloxacin tablet alone. In the didanosinecation regimen, subjects received two didanosine-placebo tablets every 12 hours for two doses. On day 2, they received two didanosine-placebo tablets immediately followed by a single 750 mg ciprofloxacin tablet. Serial blood samples were collected for 24 hours after administration of each ciprofloxacin dose. The average maximum concentration of ciprofloxacin alone was 3.38 +/- 0.63 (SD) micrograms/ml compared with 0.25 +/- 0.21 (SD) micrograms/ml when ciprofloxacin was administered with the didanosine placebo (p < 0.0001). The mean (+/- SD) area under the plasma drug concentration-time curve from time 0 to the last measurable concentration for ciprofloxacin alone was 15.50 +/- 2.69 micrograms.hr/ml compared with 0.26 +/- 0.21 micrograms.hr/ml when ciprofloxacin was coadministered with the didanosine-placebo (p < 0.0001). The mean time to maximum concentration of ciprofloxacin alone decreased from 1.56 +/- 0.62 to 0.75 +/- 0.38 hours with buffer administration (p = 0.0012). The simultaneous administration of ciprofloxacin and didanosine should be avoided.
authors.affiliation: Clinical Investigation Unit, Ottawa General Hospital, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Sahai
authors.forename: K
authors.initials: K
authors.lastname: Gallicano
authors.forename: L
authors.initials: L
authors.lastname: Oliveras
authors.forename: S
authors.initials: S
authors.lastname: Khaliq
authors.forename: N
authors.initials: N
authors.lastname: Hawley-Foss
authors.forename: G
authors.initials: G
authors.lastname: Garber
mesh_terms: D000328:Adult; D000535:Aluminum / Q000009:adverse effects; D000704:Analysis of Variance; D001682:Biological Availability; D002412:Cations / Q000009:adverse effects*; D002939:Ciprofloxacin / Q000493:pharmacokinetics*; D016049:Didanosine / Q000008:administration & dosage*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D008274:Magnesium / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012995:Solubility; D013607:Tablets
chemical_list: D002412:Cations; D013607:Tablets; D002939:Ciprofloxacin; D000535:Aluminum; D008274:Magnesium; D016049:Didanosine