Tissue distribution of methotrexate in rats. A comparison between intravenous injection as bolus or drip infusion.

Concentrations of methotrexate (MTX, 30 mg/kg) in rat sera and tissues were compared after the drug was administered by i.v. route as bolus injection or by drip infusion. Plasma and tissue specimens were collected after 1 h and 4 h and assayed for MTX by RIA. After 1 h the continuous infusion gave higher MTX levels in plasma, liver, bowel, lung, kidney, testicle and muscle; bolus injection gave higher levels in brain. No differences in levels were found in fat. After 4 h the differences between the two methods of administration were still appreciable only in liver, testicle and muscle. The differences were confirmed by determination of AUC for sera and tissue levels (1-4 h). These data suggest that continuous infusion may be more useful to obtain the highest levels of MTX in tissues with low or medium blood flow (as is probably the case in cancer tissue). Bolus injection, on the other hand, promotes the flow of the drug across the blood-brain barrier.