The influence of route of administration on the hepatic uptake of methotrexate

The present study was designed to determine if the hepatic toxicity of chronic low-dose methotrexate could be circumvented by administering the drug systemically, avoiding high initial hepatic drug exposure resulting from absorption of an oral dose into the portal circulation. Hepatic concentrations of methotrexate were determined in rats following chronic administration of 1 mg/kg by either the intraperitoneal (absorbed via the portal circulation) or subcutaneous route. Plasma drug profiles of methotrexate administered by the two routes were similar. The mean (+/- S.D.) hepatic methotrexate concentration following intraperitoneal administration was 3.12 +/- .47 nmol/gm wet weight and following subcutaneous administration it was 2.68 +/- .52 (p = .06). Renal methotrexate concentrations in the 2 groups were 1.23 +/- .27 and 1.26 +/- .49 nmol/gm wet weight, respectively (p = .88). The results of this study suggest that that oral administration does not lead to greater accumulation of methotrexate in the liver compared to systemic administration.