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Plasma and cellular adriamycin concentrations in patients with myeloma treated with ninety-six-hour continuous
Abstract:
Adriamycin (ADM) concentrations in neoplastic plasma cells, nucleated blood cells, bone marrow cells, and plasma were measured in seven patients with advanced multiple myeloma. ADM was administered as a 96-hour infusion of 9 mg/m2/24 hr. Maximum plasma ADM concentrations were 15.8 +/- 4.4 ng/ml. ADM concentrations in nucleated blood cells, bone marrow cells, and plasma cells increased continuously throughout the 96-hour infusion. Maximum cellular levels were up to 200-fold higher than the maximum plasma concentration and were similar to levels observed shortly after administration of the total dose in one rapid injection. The cellular AUC for 96-hour infusion and bolus injection were comparable. Thus continuous infusion is the equivalent of bolus injection in delivering ADM to the target cells in bone marrow, although plasma ADM concentrations remained very low. These results provide support for administering ADM as a continuous infusion with less toxicity and better patient tolerance.
Insights
Continuous infusion of Adriamycin (ADM) delivers high concentrations to bone marrow cells in multiple myeloma patients. This method is as effective as rapid injection but may reduce toxicity and improve tolerance.
Area of Science:
- Pharmacology
- Oncology
- Hematology
Background:
- Multiple myeloma is a cancer of plasma cells.
- Adriamycin (ADM) is a chemotherapy drug used in cancer treatment.
- Optimizing ADM delivery to target cells is crucial for efficacy.
Purpose of the Study:
- To compare Adriamycin (ADM) concentrations in plasma and various cell types after continuous infusion versus rapid injection.
- To evaluate the efficacy of continuous infusion for delivering ADM to neoplastic plasma cells in multiple myeloma.
Main Methods:
- Seven patients with advanced multiple myeloma received ADM via a 96-hour continuous infusion (9 mg/m2/24 hr).
- ADM concentrations were measured in plasma, nucleated blood cells, bone marrow cells, and plasma cells.
- Cellular and plasma ADM levels were compared to historical data from rapid injection studies.
Main Results:
- Maximum plasma ADM concentrations were low (15.8 +/- 4.4 ng/ml).
- Cellular ADM levels increased throughout the 96-hour infusion, reaching up to 200-fold higher than plasma concentrations.
- Cellular AUC for continuous infusion was comparable to bolus injection, indicating equivalent drug delivery to target cells.
Conclusions:
- Continuous infusion of ADM effectively delivers the drug to bone marrow cells in multiple myeloma.
- This administration method achieves similar cellular drug levels as bolus injection.
- Continuous infusion may offer reduced toxicity and improved patient tolerance for ADM therapy.