The authors of this article [Yabuuchi et al., 1998: (http://jpet.aspetjournals.org/cgi/reprint/286/3/1391)(http://www.ncbi.nlm.nih.gov/pubmed/9732402?dopt=Abstract)] describe the capacity of the type I Na(+)/Pi cotransporter (NPT1), a sodium and inorganic phosphate (Pi) transporter, to transport either organic anions, including probenecid, or inorganic phosphate (Pi) out of the liver and into the blood. Yabuuchi et al. (1998) noted that probenecid can compete with Pi for transport by NPT1, and this could conceivably mean that a higher intake of Pi might inhibit the efflux of uric acid (urate, UA), an organic anion whose reabsorption by proximal tubule epithelial cells can be inhibited by probenecid (http://scholar.google.com/scholar?hl=en&q=urate+probenecid), from the liver or otherwise influence the efflux or uptake of urate or xanthine by cells in the liver or kidneys, etc. (http://scholar.google.com/scholar?hl=en&q=%22inorganic+phosphate%22+anion+transporter). It's also conceivable that increases in extracellular or, in a more likely event, intracellular Pi could slow the elimination of antiviral drugs used to treat influenza. For example, Oo et al. (2002) [Oo et al., 2002: (http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=127254&blobtype=pdf)(http://www.ncbi.nlm.nih.gov/pubmed/12019123)] noted that the active metabolites of some neuraminidase inhibitors are mostly excreted unchanged, such as through their uptake by the proximal tubule cells, from the peritubular capillaries, and efflux across the luminal (apical) membranes of proximal tubule epithelial cells into the tubular fluid. Karie et al. (2006) [Karie et al., 2006: (http://ndt.oxfordjournals.org/cgi/reprint/21/12/3606.pdf)(http://www.ncbi.nlm.nih.gov/pubmed/16799172)] noted that some neuraminidase inhibitors do not serve as substrates for cytochrome P450 oxidoreductases in the liver and do not inhibit those enzymes either, and that's a major reason that their active metabolites are mostly excreted unchanged by renal tubular excretion. Probenecid competes with some of these These interactions would probably not be very likely and would be most likely to occur, if at all, in people whose kidney function has already been diminished, as a result of age or other factors. This is a hastily-chosen article that describes the capacity of probenecid to inhibit the transport and, hence, renal excretion of some neuraminidase inhibitors or their active metabolites [(http://www.cdc.gov/Mmwr/preview/mmwrhtml/rr4814a1.htm); (http://scholar.google.com/scholar?q=probenecid+neuraminidase+inhibitor&hl=en)], and that basically means that oral purines or phosphate supplementation could conceivably slow the elimination of some neuraminidase inhibitors, and that wouldn't necessarily be desirable. It might sound good, and some people have proposed the use of probenecid to allow for the use of neuraminidase inhibitors at lower dosages (thereby allowing more people to be treated with antivirals, in the event of a "1970's-style shortage" of antivirals). But that could be a dangerous approach, given that the movement and constant efflux of some neuraminidase inhibitors is necessary to prevent the potentially problematic effects of their accumulation intracellularly, in cells in the liver or kidneys.
Thus, if one were taking an antiviral to treat an influenza infection and also taking some oral purine compound or source of inorganic phosphate (Pi), one might need to reduce the dosages of those or, as discussed by Karie et al. (2006), reduce the dosages of the antivirals. It would seem that reducing the dosage of the antiviral would not be the better approach, in theory, but one would obviously want to discuss this with one's doctor. Some of the major old M2 protein inhibitors, used as antivirals in the treatment of influenza, are derivatives of 1-aminoadamantane and are therefore also excreted unchanged. Aminoadamantane derivatives are apparently transported by organic cation transporters and would seem to not compete with UA or phosphate, but probenecid is a weak base and can sometimes inhibit the transport of substrates of organic cation transporters (http://scholar.google.com/scholar?hl=en&q=probenecid+aminoadamantane). There are strange ways in which substrates of organic cation transporters can influence the transport of other substrates (drugs or physiological compounds) of organic anion transporters [Khamdang et al., 2002: (http://jpet.aspetjournals.org/cgi/content/full/303/2/534)(http://www.ncbi.nlm.nih.gov/pubmed/12388633?dopt=Abstract)], maybe because they, like probenecid, are weak bases and could either be protonated or deprotonated or because they contain more than one ionizable group. There can be pH extremes and variations in the tubular fluid, for example, and there could be indirect interactions. An increase in the reabsorption of UA could, for example, be pH dependent and thereby produce an indirect, pH-sensitive reduction in the excretion of a drug that UA, by its binding to an efflux transporter intracellularly, in proximal tubule cells, and relative failure to serve as a substrate for transport by that transporter, competes with for transport, etc.
Another implication is that increases in the intracellular Pi concentration could reduce the loss of purine nucleotides both by inhibiting adenosine deaminase (and by activating adenosine kinase, arguably) and by reducing the efflux of cAMP or cGMP or other purine substrates of some organic anion transporters or multidrug resistance proteins that transport purines out of cells. This might mean that phosphate could, apart from its role in promoting normal purine salvage, serve as a dose-reducing agent for oral purines, such as ATP disodium, even in the absence of an influenza infection, obviously. But that's more theoretical, and these are just my opinions. Obviously, other medications, including but not limited to some antibiotics, are transported by organic anion transporters, too, and that's another reason one should discuss this type of thing with one's doctor.
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