Influence of Omeprazole on Bioavailability of Bismuth following Administration of a Triple Capsule of Bismuth Biskalcitrate, Metronidazole, and Tetracycline

Abstract

The objective of this study was to determine the impact of omeprazole on bismuth (Bi) bioavailability when given in a three-in-one capsule containing bismuth biskalcitrate, metronidazole, and tetracycline. Thirty-four healthy volunteers were randomly assigned to receive three capsules (each containing bismuth biskalcitrate 140 mg + metronidazole 125 mg + tetracycline 125 mg) qid alone x 6 days or the same treatment + omeprazole (OM) 20 mg bid. Blood was drawn at intervals for 24 hours after the last dose. After the last dose, mean (CV) C(min) for plasma bismuth was 2882 pg/mL (36%) and 1195 pg/mL (23%) (p< 0.001), with and without OM, respectively. Mean (CV) C(max) was 25493 pg/mL (69%) and 8061 pg/mL (28%) (p < 0.001) with and without OM, respectively. AUC(0-24) increased by 2.9 in presence of OM (p < 0.001). Adverse events in both groups were usually mild and of a gastrointestinal nature, and all had resolved by the end of the trial. This study confirms an interaction between Bi biskalcitrate and OM. Risk of Bi toxicity, seen after long-term use of Bi compounds, is minimal here because plasma levels of Bi remained well below the toxic levels of 50 microg/L, and the treatment period with this triple capsule + OM is only 10 days, a substantially lower number of days compared to that which might produce Bi toxicity.

Adverse events with bismuth salts for Helicobacter pylori eradication: Systematic review and meta-analysis

“…The doses of bismuth used in H pylori eradication are administered for a much shorter duration, typically 1 to 2 wk. In a recent bioavailability study, where bismuth salts were given in combination with omeprazole for 6 d [12] , plasma levels of bismuth remained well below 50 μg/mL, but a review of their safety profile would provide additional evidence that such low doses of bismuth, given for a short period of time, do not expose patients to undue risks. We have therefore conducted a systematic review and meta-analysis of available published literature to assess the magnitude of the risk of adverse events experienced when bismuth salts are used, either alone or in combination with one or more antibiotics, to eradicate H pylori.…”

Concentrations of metronidazole in human plasma and saliva after tablet or gel administration

“…[2][3][4][5] Systemic use of Mtz for periodontal treatment has been evaluated in different oral doses: 250 mg, three times/day; [6] 400 mg, three times/day; [7][8][9] and 500 mg, three times/ day. [10,11] Mtz results in excellent oral absorption, [12] and its oral bioavailability (>90%) is commonly reported, [13,14] with tissue concentrations generally similar to or slightly lower than those measured in the serum. [15] The blood serum protein binding is 10-15%.…”

“…Right after the first collection, all volunteers had a standard breakfast and water ad libitium. Blood (5 ml) and saliva (3 ml) samples were collected 8,9,12,13,15,19,32 and 56 h after gel application.…”

“…[16] Mtz and its metabolites are mostly excreted via renal excretion, and up to 77% of the dose is recovered in the urine as unchanged drug (10%) or metabolites (90%). [15] The pharmacokinetic profile of Mtz in tablets Studies was investigated in different oral doses: 125, [12] 250, [17] 500 [18][19][20][21] and 1000 mg. [15] In addition, the pharmacokinetic of single oral dose of 750 mg Mtz tablet was observed [22] in a non-controlled study.…”

Adopting Lead‐Free Electronics: Policy Differences and Knowledge Gaps

“…trointestinal tract and in radiotherapy (Bethge et al 2003;Spenard et al 2004). A thorough examination of extensive research on the toxicity of metals and their salts has demonstrated, however, that it is not prudent to infer human and ecosystem effects across various compounds containing the same metal ion or across different environmental conditions of exposure (Dopp et al 2004).…”