Subcutaneous injection of citrate-buffered epoetin alpha (EPO-alpha) causes pain. Substitution of citrate buffer with a phosphate buffer in the EPO-alpha resulted in a significant reduction in duration and severity of pain. It is possible that sodium citrate which is present in the EPO-alpha may be the agent that causes discomfort in the patients.
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Yu et al. (1998) studied this question.
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