Oral drug absorption food, effect

Food-Effect Studies. Coadministration of food with oral drug products may influence drug BA and/or BE. Food-effect BA studies focus on the effects of food on the release of the drug substance from the drug product as well as the absorption of the drug substance. BE studies with food focus on demonstrating comparable BA between test and reference products when coadministered with meals. Usually, a single-dose, two-period, two-treatment, two-sequence crossover study is recommended for both food-effect BA and BE studies. 

In human volunteers, aprepitant showed between 59% and 67% oral bioavailability, and there was no effect of food on drug absorption.12 The compound is also a substrate and a moderate inhibitor of cytochrome P450 3A4 and an inducer of 2C9, but shows only modest 3A4 inhibition after an oral dose and modest induction of these enzymes over time in the clinic.13... 

Factors affecting drug absorption include formulation, disease state, food effect, and drug-drug interaction. Formulations used for oral administration include solutions, suspensions, capsules, and uncoated and coated tablets. Depending on the formulation of a drug, the absorption characteristics may differ substantially. 

Although formulation variables such as particle size and excipients have not been discussed here, they are highly relevant in practice. In addition, food can play an important role in oral absorption and thus bioavailability. Food may increase blood flow and thus limit the extent of first-pass effect. Bile secretion increases with food intake, which may enhance the solubility of lipophilic compounds. Attempts have been made to predict the effect of food on the extent of drug absorption [87]. Gastric emptying time is another factor, which depends on the type and the amount of food intake and physiopathology, among others. 

The BDCS should serve the needs of the earliest stages of discovery research where it can be useful in predicting routes of elimination, effects of efflux, and absorptive transporters on oral absorption, when transporter-enzyme interplay will yield clinically significant effects, such as low bioavailability and drug-drug interactions, the direction and importance of food effects, and transporter effects on postabsorption systemic levels following oral and intravenous doses. 

Since oral administration is the most common and useful, there are many opportunities in developing oral dosage forms. The oral route faces several obstacles to drug absorption, such as the first pass effect, individual variabihty of bioavailability, and drug-induced local irritation to gastric and intestinal mucosa. According to the US Food and Drug Administration (FDA) Biopharmaceutics Classification System... 

There is an increased risk of toxicity of MTX when administered with the NSAIDs, salicylates, oral antidiabetic drugs, phenytoin, tetracycline, and probenecid. There is an additive bone marrow depressant effect when administered with other drug known to depress the bone marrow or with radiation therapy. There is an increased risk for nephrotoxicity when MTX is administered with other drug that cause nephrotoxicity. When penicillamine is administered with digoxin, decreased blood levels of digoxin may occur. There is a decreased absorption of penicillamine when the dmg is administered with food, iron preparations, and antacids. 

After oral administration of 400 mg of rifaximin to fasted healthy volunteers blood drug concentration was found to be lower than the detection limit of the analytical method (i.e. 2.5 ng/ml) in half of them [102]. In the remaining subjects very low amounts were detected at some of the time intervals during the first 4 h after intake. Along the same lines, the urinary concentrations of the drug were very low and often undetectable. The effect of food on the absorption of the antibiotic was also evaluated [34] and a significant, albeit not clinically relevant, increase of bioavailabity was observed after a high-fat breakfast (table 5). 

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