Pharmacokinetics of intrapericardial administration of 5-fluorouracil.
A 30-year-old patient with metastatic breast adenocarcinoma was diagnosed as having a malignant pericardial effusion.


METHODS
The patient was treated with two courses of 200 mg 5-fluorouracil (5-FU) followed by 20 mg cisplatin 5 h later directly infused into the pericardial space through a catheter. The drug levels of the 5-FU were monitored during the second treatment. The half-life of 5-FU in the pericardial space was 168.6 min with a concentration of 0.113 mg/ml still detected at 5 h. The area under the curve (AUC) was estimated to be 4.739 mg h/ml. The plasma concentrations of 5-FU ranged from 0.022 to 0.04 mg/ml throughout the infusion.


RESULTS
There was no significant change in the patient's blood counts or chemistry profile. She did not experience any side effects during the treatment. A pericardial window was performed 2 days later when balloon pericardiectomy was unsuccessful. The patient eventually succumbed to her disease 4 months later, but without evidence of pericardial effusion.


CONCLUSIONS
We conclude that pericardial infusion of 5-FU allowed a high concentration of 5-FU to be achieved within the pericardial sac with a greatly increased half-life over that of systemic 5-FU treatment (168 min vs 6-20 min), and with little systemic toxicity.
Lerner-Tung
M B
MB
Department of Medicine, Genesee Hospital, University of Rochester, NY, USA.
Chang
A Y
AY
Ong
L S
LS
Kreiser
D
D
D000230:Adenocarcinoma / Q000150:complications / Q000188:drug therapy; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy; D002945:Cisplatin / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D017809:Fatal Outcome; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D008207:Lymphatic Metastasis; D010490:Pericardial Effusion / Q000188:drug therapy / Q000378:metabolism*; D010496:Pericardium / Q000187:drug effects / Q000378:metabolism*
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D002945:Cisplatin; D005472:Fluorouracil