Bioequivalence formula

Cholestyramine, calcium carbonate, sucralfate, aluminum hydroxide, ferrous sulfate, soybean formula, and dietary fiber supplements may impair the absorption of levothyroxine from the G1 tract. Drugs that increase nondeiodinative T4 clearance include rifampin, carbamazepine, and possibly phenytoin. Amiodarone may block the conversion of T4 to T3. Thyroid, USP (or desiccated thyroid) is derived from hog, beef, or sheep thyroid gland. It may he antigenic in allergic or sensitive patients. Inexpensive generic brands may not be bioequivalent. 

Even after an application has been approved and the product has been marketed, consideration should be given to the effects of changes in the manufacturing formula or manufacturing process. Bioequivalence of the product and the stability properties may be affected. Appropriate studies will therefore need to be conducted, and applications for the changes will need to be submitted as necessary. 

It has been known for several years through in vivo tracer studies that human term and preterm infants are capable of synthesizing C20 and C22 LCP from the Cjg precursors (Carnielli et al., 1996 Salem et al., 1996 Sauerwald et al., 1997). These and more recent studies suggest that this capability is highly variable from individual to individual (Uauy et al., 2000). However, all studies to date have sampled blood compartments, and estimates of relative conversion based on such measurements are tenuous at best. We recently reported the bioequivalence of dietary LN A and DHA as precursors for primate neonate brain DHA accretion based on direct measurements of brain DHA accretion (Su et al., 1999a). Neonate baboons were fed a commercial infant formula with 18% of total fatty acids by weight as LA and 1.8% as LNA, which gives an LA/LNA ratio of 10 for 6 wk. Doses of LNA or DHA were administered orally at 4 wk and animals were sacrificed at 6 wk. 

The term bioequivalence, as used here, is chosen to imply a relative efficacy in accretion between two sources of brain DHA, in analogy to the use of the term in reference, for instance, to retinol and fl-carotene. The crucial clinical issue for infant formulations is to establish the amount of DHA to be added to LCP-free formulas as a precursor for neonate brain development. In our neonate study, the commercial formula contained 1.8% of calories as LNA, and the only dietary DHA that these animals consumed was from the dose. Thus, the bioequivalence of 7 1 applies directly to the addition of small amounts of DHA to formula, meaning that the addition of DHA at 0.26% of calories may provide an equal amount of brain DHA as the entire 1.8% calories as LNA. Factors driving the addition of less DHA include possible interference with A A metabolism, the possibility of contaminants added incidentally in DHA oils, and expense. The potency of DHA relative to LNA suggests that the addition of amounts as small as 0.1% of calories would support brain growth, a figure similar to the lowest levels of DHA found inhuman breast milk. Finally, we note that the purely biochemical nature of our studies to date cannot establish whether LNA can completely substitute for DHA. Studies in human preterms suggest that it cannot, whereas those in term infants remain controversial (Cunnane, Francescutti, Brenna, Crawford, 2000). 

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