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Urine alkalinization prior to administering high doses of Methotrexate is crucial primarily to prevent crystallization. Methotrexate is a cytotoxic chemotherapy agent that can exist in a crystalline form within the renal tubules if urine is acidic. This crystallization can lead to obstructive nephropathy and renal damage, potentially leading to severe toxicity and reduced clearance of the drug from the body. By alkalinizing the urine through the administration of agents such as sodium bicarbonate, the solubility of Methotrexate is increased, helping to ensure that it remains in a dissolved state, minimizing the risk of crystallization in the kidneys and promoting safer excretion.

The other options listed, such as increasing drug efficacy, reducing toxicity in a general sense, or enhancing absorption, are less relevant in the context of Methotrexate and urine alkalinization. While reducing toxicity and increasing efficacy can be important considerations in drug administration, they do not specifically address the direct consequence of crystallization in the renal system that the alkalinization aims to prevent. Therefore, prevention of crystallization is the primary rationale for this practice.