Effect of bismuth subsalicylate on ciprofloxacin bioavailability

Abstract

A single oral dose of 528 mg of bismuth subsalicylate (30 ml of Pepto-Bismol) had no significant elect on the plasma pharmacokinetics of a single oral dose of 750 mg of ciprofloxacin administered to 12 healthy volunteers (six men and six women). These results suggest that ciprofloxacin bioavailability will not be significantly decreased by single doses of bismuth subsalicylate when the two medications are administered simultaneously.Development of the fluoroquinolones has allowed oral treatment of serious infections which until a few years ago required parenteral therapy (8). Although many of these agents are absorbed well from the gastrointestinal tract, their bioavailability is reduced significantly when administered with antacids containing di-and trivalent metal cations (10,12,16,17). This has resulted in therapeutic failure in at least one instance (11). The exact mechanism of this interaction has not been elucidated fully, although complexation with the metal ions (13-15) and adsorption to the antacids (19, 20) are suggested mechanisms.Bismuth, a heavy metal, can exist as a trivalent cation. Bismuth subsalicylate (Pepto-Bismol) is commonly used for the symptomatic treatment and prevention of a variety of gastrointestinal disorders. Bismuth subsalicylate decreases the bioavailability of tetracyclines significantly, and recommendations have been made for separation of the dosing times for these two medications (1, 4). However, preliminary studies evaluating the interaction of bismuth salts on norfloxacin and ciprofloxacin absorption have demonstrated only minor reductions in fluoroquinolone bioavailability (3,18). These data are in distinct contrast to those observed when ciprofloxacin is administered concurrently with other trivalent cations, such as aluminum. Because patients are likely to receive bismuthcontaining compounds concurrently with fluoroquinolones, among which ciprofloxacin is well established, this study was conducted to determine the effect of a single dose of bismuth subsalicylate on ciprofloxacin absorption in healthy volunteers.This study was approved by the Human Experimental Procedures Committee, Ottawa General Hospital, Ottawa, Ontario, Canada. Written informed consent was obtained from 12 healthy volunteers (six men and six women). The mean (± standard deviation) age and weight of the subjects were 35 ± 8 years and 70 ± 11 kg, respectively. Volunteers were excluded on the basis of the following: pregnancy, hypersensitivity reactions to any drug, use of any medications, chronic illness, current infection, abnormal finding on physical examination, abnormal renal or hepatic function tests, and abnormal hematology or urinalysis. On the morning of each study day, subjects were admitted to the Clinical Investigation Unit, Ottawa General Hospital.The study design was a randomized, two-period, two-treat- ment, two-sequence crossover with a 7-day washout period. Subjects were instructed to fast overnight and were not allowed to eat until 4 h after administration of the study medications. In on...

In vitro–in vivo studies of the quantitative effect of calcium, multivitamins and milk on single dose ciprofloxacin bioavailability

“…Prolonged antibiotic therapy causes anemia, gastric irritation or acidity; thus, antacids and multi-vitamin formulations are the commonly co-administered drugs with antibiotics [1] , [5] , [8] . Calcium either in the form of carbonate or chloride is a constituent of many marketed antacid formulations [2] , [3] , [42] , [43] . Multivitamin formulations, especially with mineral contents, are found to reduce the bioavailability of fluoroquinolones [4] , [5] , [8] .…”

“…Owing to such ionization, the exposed and negatively charged groups on CPFX bind with the positively charged Ca 2+ ions that are present in the medication or supplement administered, referred to as chelation. The degree or significance of this interaction is, however, dependent on the time of exposure to one another and the pH of the environment at that time [2] , [13] , [24] , [26] , [41] , [42] , [43] , [44] . A 2 h separation of the calcium containing products and the CPFX can avoid this interaction.…”

Rifabutin Containing Triple Therapy and Rifabutin with Bismuth Containing Quadruple Therapy for Third‐Line Treatment of Helicobacter pylori Infection: Two Pilot Studies

“…Bismuth salts were administered at 11.00 AM and 11.00 PM, that is three hours after amoxicillin and rifabutin, since they may bind with the antibiotics, a process that may reduce their full absorption [37,38].…”

Fluoroquinolones, the Cornerstone of Treatment of Drug-Resistant Tuberculosis: A Pharmacokinetic and Pharmacodynamic Approach

“…In healthy volunteers (n=12), the complexation of Bi 3+ , the metallic ion present in bismutsubsalicylate, with CFX was probably not stable enough to significantly decrease CFX absorption given the marginal decrease in CFX AUC and C max (297). Sevelamer hydrochloride is a phosphate binding cationic polymer that can almost halve the CFX exposure upon co-administration (291).…”