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A phase I and pharmacokinetic study of MAG-CPT, a water-soluble polymer conjugate of camptothecin.

Schoemaker NE, van Kesteren C, Rosing H, Jansen S, Swart M, Lieverst J, Fraier D, Breda M, Pellizzoni C, Spinelli R, Grazia Porro M, Beijnen JH, Schellens JH, ten Bokkel Huinink WW - Br. J. Cancer (2002)

Bottom Line: MAG-CPT and free camptothecin were accumulated during days 1-3 and considerable amounts of MAG-CPT could still be retrieved in plasma and urine after 4-5 weeks.The half-lives of bound and free camptothecin were equal indicating that the kinetics of free camptothecin were release rate dependent.In summary, the pharmacokinetics of camptothecin were dramatically changed, showing controlled prolonged exposure of camptothecin.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Antoni van Leeuwenhoek Hospital/The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. apnsc@slz.nl

ABSTRACT
Polymeric drug conjugates are a new and experimental class of drug delivery systems with pharmacokinetic promises. The antineoplastic drug camptothecin was linked to a water-soluble polymeric backbone (MAG-CPT) and administrated as a 30 min infusion over 3 consecutive days every 4 weeks to patients with malignant solid tumours. The objectives of our study were to determine the maximal tolerated dose, the dose-limiting toxicities, and the plasma and urine pharmacokinetics of MAG-CPT, and to document anti-tumour activity. The starting dose was 17 mg m(-2) day(-1). Sixteen patients received 39 courses at seven dose levels. Maximal tolerated dose was at 68 mg m(-2) day(-1) and dose-limiting toxicities consisted of cumulative bladder toxicity. MAG-CPT and free camptothecin were accumulated during days 1-3 and considerable amounts of MAG-CPT could still be retrieved in plasma and urine after 4-5 weeks. The half-lives of bound and free camptothecin were equal indicating that the kinetics of free camptothecin were release rate dependent. In summary, the pharmacokinetics of camptothecin were dramatically changed, showing controlled prolonged exposure of camptothecin. Haematological toxicity was relatively mild, but serious bladder toxicity was encountered which is typical for camptothecin and was found dose limiting.

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Related in: MedlinePlus

Plot of AUC∞ of bound camptothecin (left panel) and free camptothecin (right panel) as a function of the accumulative administered dose of MAG-CPT during course 1. Bars indicate mean values.
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fig3: Plot of AUC∞ of bound camptothecin (left panel) and free camptothecin (right panel) as a function of the accumulative administered dose of MAG-CPT during course 1. Bars indicate mean values.

Mentions: Mean plasma concentration-time curves of bound campto thecin and free camptothecin of patients treated with 68 mg m−2 day−1 MAG-CPT.


A phase I and pharmacokinetic study of MAG-CPT, a water-soluble polymer conjugate of camptothecin.

Schoemaker NE, van Kesteren C, Rosing H, Jansen S, Swart M, Lieverst J, Fraier D, Breda M, Pellizzoni C, Spinelli R, Grazia Porro M, Beijnen JH, Schellens JH, ten Bokkel Huinink WW - Br. J. Cancer (2002)

Plot of AUC∞ of bound camptothecin (left panel) and free camptothecin (right panel) as a function of the accumulative administered dose of MAG-CPT during course 1. Bars indicate mean values.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2364251&req=5

fig3: Plot of AUC∞ of bound camptothecin (left panel) and free camptothecin (right panel) as a function of the accumulative administered dose of MAG-CPT during course 1. Bars indicate mean values.
Mentions: Mean plasma concentration-time curves of bound campto thecin and free camptothecin of patients treated with 68 mg m−2 day−1 MAG-CPT.

Bottom Line: MAG-CPT and free camptothecin were accumulated during days 1-3 and considerable amounts of MAG-CPT could still be retrieved in plasma and urine after 4-5 weeks.The half-lives of bound and free camptothecin were equal indicating that the kinetics of free camptothecin were release rate dependent.In summary, the pharmacokinetics of camptothecin were dramatically changed, showing controlled prolonged exposure of camptothecin.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Antoni van Leeuwenhoek Hospital/The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. apnsc@slz.nl

ABSTRACT
Polymeric drug conjugates are a new and experimental class of drug delivery systems with pharmacokinetic promises. The antineoplastic drug camptothecin was linked to a water-soluble polymeric backbone (MAG-CPT) and administrated as a 30 min infusion over 3 consecutive days every 4 weeks to patients with malignant solid tumours. The objectives of our study were to determine the maximal tolerated dose, the dose-limiting toxicities, and the plasma and urine pharmacokinetics of MAG-CPT, and to document anti-tumour activity. The starting dose was 17 mg m(-2) day(-1). Sixteen patients received 39 courses at seven dose levels. Maximal tolerated dose was at 68 mg m(-2) day(-1) and dose-limiting toxicities consisted of cumulative bladder toxicity. MAG-CPT and free camptothecin were accumulated during days 1-3 and considerable amounts of MAG-CPT could still be retrieved in plasma and urine after 4-5 weeks. The half-lives of bound and free camptothecin were equal indicating that the kinetics of free camptothecin were release rate dependent. In summary, the pharmacokinetics of camptothecin were dramatically changed, showing controlled prolonged exposure of camptothecin. Haematological toxicity was relatively mild, but serious bladder toxicity was encountered which is typical for camptothecin and was found dose limiting.

Show MeSH
Related in: MedlinePlus