Pharmacokinetics of methotrexate in adult Indian patients and its relationship to nutritional status

Since anticancer drugs have a low therapeutic index, any significant change in the pharmacokinetics of a drug would have a bearing on therapeutic efficacy and drug toxicity. Nutritional deficiencies have been shown to affect the four processes of pharmacokinetics, ie, absorption, distribution, biotransformation, and excretion. Malnutrition and undernutrition are widely prevalent in India and thus it was thought to be of practical importance to study the effect of initial nutritional status on the overall kinetics of methotrexate, a widely used anticancer drug. The results of the study reveal that relative weight correlates well with the anthropometric parameters, nutritional parameters, and dietary intake and may be used as a marker of nutritional status. When grouped on the basis of relative weights, the undernourished patients revealed a significant (P less than 0.01) prolongation of biological half-life and a significant (P less than 0.001) reduction in clearance. Based on these results, relative weight has been proposed as a basis for drug dosage determinations in place of the existing practice of administering antineoplastic drugs on the basis of body surface area or body weight alone.