Effect of sucralfate on absorption of norfloxacin and ofloxacin

Abstract

The effect of sucralfate on the pharmacokinetics of norfloxacin and ofloxacin was assessed in two separate crossover studies with healthy volunteers. In both studies, eight subjects were randomized to one of the following three regimens: a 400-mg dose of norfloxacin or ofloxacin alone, norfloxacin or ofloxacin given simultaneously with sucralfate (1 g), or norfloxacin or ofloxacin given 2 h before sucralfate. Coadministration of sucralfate reduced the bioavailability of norfloxacin and ofloxacin by 91% (P < 0.001) and 61% (P < 0.001), respectively. However, when norfloxacin and ofloxacin were given 2 h before sucralfate, there were no significant alterations in the pharmacokinetics of either fluoroquinolone. Similar results were obtained when the cumulative amount of each fluoroquinolone recovered in the urine was used to calculate bioavailability. To avoid these interactions and potential therapeutic failures, norfloxacin and ofloxacin should not be used concurrently with sucralfate. The interaction can be minimized by maximizing the time between the fluoroquinolone dose and the previous sucralfate dose and giving the fluoroquinolone at least 2 h before another sucralfate dose.Antacids and sucralfate are known to impair the absorption of fluoroquinolone antimicrobial agents from the gastrointestinal tract by formation of nonabsorbable chelate complexes (1-4, 10, 11, 15-17). Sucralfate has been shown to decrease the absorption of, e.g., ciprofloxacin (3, 15), norfloxacin (17), and fleroxacin (11). The bioavailability of ciprofloxacin and norfloxacin was reduced by about 90% when they were administered with sucralfate. However, coadministration of fleroxacin with sucralfate only slightly decreased the absorption of the former. To our knowledge, there is no published study on the effect of sucralfate on the absorption of ofloxacin.It has been demonstrated that the interaction with sucralfate can be decreased by staggering the administration times of sucralfate and a fluoroquinolone (15, 17). However, in these studies, sucralfate was given before the fluoroquinolone dose, which may not be the best approach. In addition to the length of the interval separating the intake of a fluoroquinolone and a drug containing cations, the sequence in which the drugs are ingested is important.The purposes of this investigation were to study the effect of sucralfate on the absorption of ofloxacin and norfloxacin and to determine whether probable interactions could be prevented by giving the fluoroquinolone dose 2 h before sucralfate. MATERIALS AND METHODSSubjects and study design. Two separate randomized threeperiod crossover studies were performed. Treatments were separated by a 7-day washout period. A total of 16 volunteers were recruited to participate in this investigation. The subjects were determined to be healthy on the basis of medical history, physical examination, and laboratory tests. They were thoroughly informed in writing, and verbal consent was obtained. [Medipolar, Oulu, Finland]), or norfloxacin alone followed by...

Elimination of Fecal Enterobacteriaceae by Intravenous Ciprofloxacin Is not Inhibited by Concomitant Sucralfate - a Microbiological and Pharmacokinetic Study in Patients

“…The interaction is further facilitated by the lack of a substituent at the 5-position of ciprofloxacin [44]. Several studies have shown that this interaction is less pronounced with other fluoroquinolones such as norfloxacin, ofloxacin, levofloxacin, lomefloxacin, fleroxacin, or sparfloxacin [45][46][47][48][49].…”

Selektive Darmdekontamination in der Intensivmedizin

“…Nur 2 h nach der gastralen Zufuhr von Ofloxacin wurde Sucralfat als Stressblutungsprophylaxe appliziert. Dieses Intervall ist zu kurz, um bei Intensivpatienten eine Bindung und damit partielle Inaktivierung von Ofloxacin durch Sucralfat im Magen auszuschließen [31,45]. Als weitere Prophylaxe wurde lediglich Amphotericin B topisch appliziert.…”

Effects of Sucralfate, Magnesium Oxide and Sodium Ferrous Citrate on Sparfloxacin Pharmacokinetics.

“…Previously, the interaction between the fluoroquinolones such as norfloxacin [7,17], ofloxacin [15,17], ciprofloxacin [3-6, 9, 10], lomefloxacin [11,16], DR-3355 (levofloxacin) [12] and fleroxacin [14,18] and cations has been reported. Shimada et al [19] studied the effect of antacid (dried aluminum hydroxide gel) on sparfloxacin gastrointestinal absorption, and found that it was the least inhibited by interaction with an antacid, compared with other new quinolones.…”

“…[7,17], ofloxacin [15,17], ciprofloxacin [3-6, 9, 10], lomefloxacin [11,16], DR-3355 (levofloxacin) [12], fleroxacin [14,18], and sparfloxacin [19][20][21][22][23] is decreased by concomitant administration of metal cation containing drugs. Therefore, the interaction between sparfloxacin and sucralfate can be explained primarily by the inhibition of absorption of sparfloxacin.…”

“…Lehto et al [17] has reported that co-administration of sucralfate with norfloxacin and ofloxacin reduced the relative bioavailability of these fluoroquinolones by 91 and 61%, respectively. Lubowski et al [14] has reported that the relative bioavailability of fleroxacin given with sucralfate was 76% compared with that of fleroxacin alone.…”