Compensation of dietary induced reduction of tetracycline absorption by simultaneous administration of EDTA

The influence of drug-drug and drug-food interactions affecting the absorption of orally administered medication is reviewed. Drug-drug interactions can be classified in terms of indirect effects by one drug on gastrointestinal tract physiology influencing the absorption of other drugs, or direct interactions involving altered pH, adsorption, absorption, or chelation. Most, but not all, drug-drug interactions result in reduced or delayed systemic drug availability. Drug-food interactions may result in reduced, delayed, or increased systemic drug availability. The absorption of only a small number of drugs is unaffected by concomitant food intake. The degree of interaction and whether it positively or negatively affects drug absorption depends on a number of factors including the physical and chemical nature of the drug, the formulation, the type of meal, and the time interval between eating and dosing. Mechanisms of drug-food interactions are not well characterised. They clearly involve both direct and indirect factors in a similar fashion to drug-drug interactions, but indirect factors probably predominate. Reduced or delayed drug absorption is generally attributed, at least in part, to delayed stomach-emptying due to food. Increased absorption may also result from delayed stomach-emptying facilitating greater drug dissolution before it passes from the stomach into the small intestine. Increased bioavailability of some drugs, e.g. propranolol, metoprolol and labetalol, may be related to reduced presystemic clearance. The potential clinical implications of drug-drug and drug-food interactions must be taken into account with oral medications in order to minimise variations in systemic drug availability and hence in clinical efficacy.

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“…(1974) Kahela et al (1979) Neuvonen et al (1971; Welling et a\. (1977b); Poiger and Schlatter (1978) Kappas et al (1978) Talbot and Meade (1971) …”

Section: Referencementioning

confidence: 95%

Interactions Affecting Drug Absorption

Welling¹

1984

Clinical Pharmacokinetics

157

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“…Therefore, EDTA-treated TJ-34 was coadministered with TC to clarify the contribution of metal ions contained in TJ-34 dried extract. Poiger and Schlatter [18] have reported the effect of EDTA on interaction between orally administered milk and TC. Coadministration of milk (200 ml) significantly reduced the f e of TC (500 mg).…”

Section: Discussionmentioning

confidence: 98%

“…However, the molar ratio of EDTA and TC was much higher (4.8:1) in their study compared to that in the present study (1.2:1). On the other hand, there are reports on reduced absorption of TC by coadministration of EDTA [18,19]. Poiger and Schlatter [18] have discussed the fact that the disodium salt of EDTA, due to its acidity, causes diarrhea, usually leading to reduced absorption of the drugs.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, there are reports on reduced absorption of TC by coadministration of EDTA [18,19]. Poiger and Schlatter [18] have discussed the fact that the disodium salt of EDTA, due to its acidity, causes diarrhea, usually leading to reduced absorption of the drugs. The slight decrease in plasma concentrations of TC observed between TC alone group (vehicle group) and coadministration of EDTAtreated TJ-34 group may be explained by this fact, but apparent diarrhea was not observed in the present study.…”

Section: Discussionmentioning

confidence: 99%

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Mechanism of drug interaction between a Kampo medicine, byakkokaninjinto, and tetracycline in rats

Hitoshi

Katoh

Tanaka

et al. 2012

Journal of Infection and Chemotherapy

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“…A classic example of a food—drug interaction resulting in decreased bioavailability with eventual treatment failure is that of tetracycline administration with milk. The calcium ions present in milk sequester the tetracycline, thereby decreasing its absorption from the gastrointestinal (GI) tract and leading to subtherapeutic systemic exposures, predisposing patients to treatment failure 7 . Another important food—drug interaction involves the effects of food or its constituents on metabolic enzyme activity.…”

mentioning

confidence: 99%

Effect of a High‐Fat Meal on the Pharmacokinetics of Saxagliptin in Healthy Subjects

Patel

Zhang

et al. 2010

The Journal of Clinical Pharma

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1211S axagliptin is a potent, selective dipeptidyl peptidase-4 (DPP-4) inhibitor, specifically designed for extended inhibition of the DPP-4 enzyme. DPP-4 is an enzyme that selectively cleaves dipeptides such as the key insulinotropic hormone glucagonlike peptide-1 (GLP-1), converting it from the intact and active form to the inactive form, and is responsible for the short half-life of intact GLP-1 in vivo. 1 Inhibitors of DPP-4 increase levels of endogenous intact GLP-1 and prolong its physiological actions, augmenting postprandial insulin secretion and improving the glycemic profile in patients with type 2 diabetes. 2 Because GLP-1 stimulates insulin secretion in a glucose-dependent manner, DPP-4 inhibitors are expected to present lower risks of hypoglycemia and may not lead to weight gain.Saxagliptin is a Biopharmaceutics Classification System (BCS) class III compound (high solubility/low permeability) but exhibits class-I−like characteristics. Clinical studies have shown that saxagliptin is rapidly and almost completely absorbed following oral administration. 3 Saxagliptin is metabolized by cytochrome P450 enzymes 3A4 and 3A5 (CYP3A4 and CYP3A5) to the pharmacologically active major metabolite BMS-510849. 4 In vitro experiments indicate that saxagliptin is a weak substrate for the efflux transporter P-glycoprotein (P-gp). 5 The terminal half-life of saxagliptin in humans is approximately 2.5 hours. 3 Food-drug interactions can result in 2 predominant clinical effects. The first is decreased bioavailability, resulting in the increased possibility of treatment failure; conversely, there is the possibility of increased bioavailability, with increased risk of adverse events and toxicities. 6 A classic example of a food-drug interaction resulting in decreased bioavailability with eventual treatment failure is that of tetracycline administration with milk. The calcium ions present in milk sequester the tetracycline, thereby decreasing its absorption from the gastrointestinal (GI) tract and leading to subtherapeutic systemic exposures, predisposing patients to treatment failure. 7 Another important food-drug interaction involves the effects of food or its constituents on metabolic enzyme activity. Most commonly observed with foods such as grapefruit juice, red wine, and tea are metabolic CYP3A4-based food-drug interactions. These foods contain furanocoumarins and flavonoids, which have been shown to inhibit the CYP3A4 enzyme system, 8 consequently slowing drug metabolism and increasing systemic drug exposure.In a preliminary study with a capsule formulation of saxagliptin, administration of single oral doses of 5 to 20 mg of saxagliptin following a highfat meal resulted in modest effects, including a maximum decrease of 28% in the maximum (peak) plasma drug concentration (C max ) of saxagliptin and a 32% increase in the area under the plasma concentration-time curve from time zero to infinity (AUC ∞ ) of saxagliptin compared with the fasted state. The time to reach C max (T max ) was increased by approximately 1.25...

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Compensation of dietary induced reduction of tetracycline absorption by simultaneous administration of EDTA

Cited by 13 publications

References 8 publications

Interactions Affecting Drug Absorption

Interactions Affecting Drug Absorption

Mechanism of drug interaction between a Kampo medicine, byakkokaninjinto, and tetracycline in rats

Effect of a High‐Fat Meal on the Pharmacokinetics of Saxagliptin in Healthy Subjects

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