Absorption

The absorption of drug and nutritional supplements can be reduced or slowed in the CKD patient due to delayed gastric emptying. Given that diabetes mellitus is a common cause of CKD, diabetic gastroparesis is a frequent comorbidity. Delayed gastric emptying will alter the absorption profile of orally administered drugs. The absorption of many drugs is affected by gastric pH. Gastric acidity is reduced in predialysis CKD patients compared to controls [6]. Gastric acidity is further mitigated by the ubiquitous use of phosphate-binding antacids by CKD patients. A practical clinical example in which there is an absorption alteration in CKD patients is when furo-semide is prescribed in a predialysis CKD patient and a blunted effect is observed. Patients with CKD do not have a particularly high bioavailability of furosemide [7]. Similarly, oral ferrous sulfate is frequently prescribed to CKD patients in combination with erythropoietic agents. Oral ferrous sulfate is poorly absorbed in an alkaline gastric environment, especially when administered concomi-tantly with oral antacids like calcium carbonate [8]. Further, oral ferrous sulfate frequently causes gastrointestinal pain. Unfortunately, when these patients complain to pharmacists and clinicians about their iron-induced gastrointestinal pain, they are frequently told to take the iron simultaneously with food or milk. This maneuver may well reduce the gastrointestinal pain, but probably it reduces the actual iron absorption to almost nothing because elements in food and milk bind to iron and food and milk raise gastric pH.

A cornerstone of the treatment of CKD patients is the use of phosphate-binding agents. Aluminum is rarely used any more, but calcium, magnesium, and lanthanum-based agents all pose the possibility of chelation of drugs as well as the intended gastrointestinal phosphorus. Tetracycline chelation to antacids is well known to clinicians, but tetracycline is not used often in the CKD patient population. Of more importance to caregivers of CKD patients is the well-described drug interaction of fluoroquinolones (e.g. ciprofloxacin, levofloxacin, ofloxacin, etc.) and metal-based phosphate-binding antacids. In a study by our research group, oral cipro-floxacin bioavailability was reduced by 51% when given simultaneously with four 667-mg calcium acetate tablets [9]. It is not only that there is a reduction in the percent of the fluoroquinolone absorbed that is a problem. The pharmacodynamics of fluoroquinolones suggest that they are more effective when high peak serum concentrations are achieved. This drug interaction also slows the rate of fluoroquinolone absorption, possibly reducing their efficacy. We have witnessed oral fluoroquino-lone treatment failures that are ascribed to this drug interaction.

It is not only the metal-based phosphate-binding antacids that may cause changes in absorption. Oral cipro-floxacin's bioavailability is also reduced by nearly half when co-administered with seven 403-mg sevelamer hydrochloride capsules [9]. The typically prescribed remedy to mitigate this interaction is to space the fluoroquinolone and any phosphate-binding agent by at least 3 h.

Another underappreciated drug interaction related to absorption in CKD patients is between prescribed nutritional products and prescribed medications. Malnutrition is the harbinger of poor therapeutic outcome in CKD patients and very precise nutritional guidelines have been established to determine when to administer nutritional supplementation to CKD patients [10]. Often this means using commercially available enteral feeding products, some of which have been especially developed for patients with CKD. However, again using fluoroquinolones as an example, it should be noted that these products contain substantial calcium, magnesium and other elements that can cause significant alterations in bioavailability. For example, our research group found that one can of an en-teral feeding product drunk at the same time as an oral fluoroquinolone was ingested, reduced the absorption of ciprofloxacin by an average of 28% and reduced ofloxacin absorption by an average of 10% [11]. Interestingly, gati-floxacin was found to have almost no change in absorption when administered with an enteral feeding product given via nasogastric tube [12].

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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