Rapid plasma clearance and reduced rate and extent of urinary elimination of parenterally administered methotrexate as a result of severe vomiting and diarrhoea.

A patient received 200 mg methotrexate IM as part of a treatment schedule for malignant melanoma. Severe vomiting and diarrhoea began shortly after treatment and persisted for 4 h. During this period the methotrexate renal clearance rate was 37 ml . min-1, increasing to 97 ml . min-1 when vomiting and diarrhoea ceased. Only 26% of the administered dose was recovered in the urine up to 48 h after treatment, whilst the plasma clearance of methotrexate assessed over the same period was 208 ml . min-1. We conclude that a considerable proportion of the dose was lost from the gastrointestinal tract during the period of vomiting and diarrhoea, and that consequently enterohepatic circulation of methotrexate plays an important role in the pharmacokinetics of the drug.