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Pharmacokinetics of intraarterial mitomycin C in humans
Abstract:
The pharmacological advantage of mitomycin C (MMC) given by intraarterial infusion as compared to i.v. infusion was studied in seven patients with cancer metastatic to the liver. Hepatic artery, hepatic vein, and peripheral vein catheters were placed, and then each patient received constant infusions of MMC via the intraarterial and peripheral i.v. routes at 0.4, 1.2, and 4.0 mg/sq m/hr. MMC concentrations were measured in the hepatic artery, hepatic vein, and a peripheral vein by high-pressure liquid chromatography after steady state had been reached at 2 hr. Mean plasma clearance increased significantly with infusion rate from 0.6 liter/min at 0.4 mg/sq m/hr to 1.1 liters/min at 4.0 mg/sq m/hr. The calculated relative advantage of treating hepatic tumors via the intraarterial route (Rt) was found to be 2.5- to 3.6-fold at a plasma flow rate of 0.4 liter/sq m and MMC infusion rates of 0.4 to 4.0 mg/sq m/hr. The hepatic vein MMC concentration averaged 30% higher during intraarterial than during i.v. infusion. Hepatic extraction of MMC averaged only 23%, so that the intraarterial route offered little advantage with respect to reduced systemic toxicity. These data suggest a limited pharmacological rationale for the selection of the intraarterial route for the treatment of hepatic tumors with MMC.
Insights
Intraarterial mitomycin C (MMC) infusion for liver cancer showed limited advantage over i.v. routes. The hepatic extraction of MMC was low, offering minimal reduction in systemic toxicity for hepatic tumors.
Area of Science:
- Oncology
- Pharmacology
- Medical Imaging
Background:
- Liver metastases often require targeted therapies.
- Intraarterial chemotherapy aims to increase drug concentration at the tumor site.
- Mitomycin C (MMC) is used in cancer treatment.
Purpose of the Study:
- To compare the pharmacological advantage of intraarterial versus intravenous (i.v.) infusion of mitomycin C (MMC) in patients with liver cancer metastases.
- To evaluate the efficacy of intraarterial MMC in delivering higher concentrations to hepatic tumors while minimizing systemic exposure.
Main Methods:
- Seven patients with liver metastases received intraarterial and i.v. infusions of MMC at varying rates.
- Catheters were placed in the hepatic artery, hepatic vein, and a peripheral vein.
- MMC concentrations were measured using high-pressure liquid chromatography (HPLC).
Main Results:
- Plasma clearance of MMC increased significantly with infusion rate.
- The intraarterial route showed a 2.5- to 3.6-fold advantage in delivering MMC to hepatic tumors.
- Hepatic vein MMC concentrations were 30% higher with intraarterial infusion.
- Hepatic extraction of MMC was only 23%, indicating limited reduction in systemic toxicity.
Conclusions:
- The intraarterial route for MMC in liver metastases offers a limited pharmacological advantage.
- Low hepatic extraction suggests minimal benefit in reducing systemic toxicity.
- The selection of the intraarterial route for MMC treatment of hepatic tumors has a limited rationale based on these findings.