Reduced systemic drug exposure by combining intra-arterial chemotherapy with hemoperfusion of regional venous drainage.
Four patients with malignant cerebral gliomas received 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) into the internal carotid artery (ICA) while the ipsilateral jugular drainage was pumped extracorporeally through a hemoperfusion cartridge containing a nonionic adsorbant resin. Each patient received 220 mg/sq m BCNU, infused over 45 minutes through a toposcopic catheter positioned with the tip in the ICA beyond the origin of the ophthalmic artery. Jugular blood was pumped extracorporeally at 300 ml/min through a large-bore catheter in the jugular bulb. Plasma samples were obtained for BCNU measurement at frequent intervals from the right atrium. During a separate treatment, 6 weeks before or after the hemoperfusion treatment, the same dose of BCNU was infused into the ICA and atrial samples were obtained on a similar schedule. Hemoperfusion of the jugular blood during intracarotid infusion reduced the systemic exposure by 56% to 87% and increased total body clearance of BCNU by two- to eightfold. The calculated pharmacokinetic advantage (brain:body exposure ratio) was between 21 and 55:1 when the combined treatment was used.
D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000188:drug therapy / Q000628:therapy*; D002330:Carmustine / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D005112:Extracorporeal Circulation; D005260:Female; D005910:Glioma / Q000188:drug therapy / Q000628:therapy*; D006464:Hemoperfusion; D006801:Humans; D007261:Infusions, Intra-Arterial; D007601:Jugular Veins; D007700:Kinetics; D008297:Male
D002330:Carmustine