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Abstract

Clinical pharmacology of polyethylene glycol-L-asparaginase.

D H Ho, N S Brown, A Yen, R Holmes, M Keating, A Abuchowski, R A Newman and I H Krakoff
Drug Metabolism and Disposition May 1986, 14 (3) 349-352;
D H Ho
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N S Brown
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A Yen
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R Holmes
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M Keating
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A Abuchowski
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R A Newman
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I H Krakoff
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Abstract

Polyethylene glycol (PEG)-L-asparaginase, at doses ranging from 500 to 8000 units/m2, was infused iv over 60 min in 31 patients of whom 27 were evaluable pharmacokinetically. The plasma disappearance of PEG-L-asparaginase is described by a monophasic curve with a mean half-life of 357 +/- 243 hr which is much longer than that of the unconjugated enzyme (half-life of approximately 20 hr). The rate of total clearance (128 +/- 74 ml/m2 X day) is much slower than that of L-asparaginase (2196 +/- 1098 ml/m2 X day). The volume of distribution is 2093 +/- 643 ml/m2, which is similar to that of L-asparaginase, indicating that PEG-L-asparaginase is mainly localized in the plasma. No enzyme could be measured in urine samples taken from nine patients for a period of up to 4 days. Additionally, no enzyme was measurable in one patient's pleural fluid obtained at the end of infusion and 6 days after infusion of a 1000-unit/m2 dose; the corresponding concentrations in plasma were 0.64 and 0.62 units/ml, respectively. In general, the plasma enzyme concentrations at the end of the 1-hr infusion and at 14 days after drug administration were proportional to the dose given. However, in two patients, a sudden disappearance of enzyme levels occurred which preceded anaphylactic reactions during subsequent treatment. A third patient developed severe bronchospasm 30 min after the first dose, but his enzyme levels were within the normal range.

 

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Drug Metabolism and Disposition
Vol. 14, Issue 3
1 May 1986
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Abstract

Clinical pharmacology of polyethylene glycol-L-asparaginase.

D H Ho, N S Brown, A Yen, R Holmes, M Keating, A Abuchowski, R A Newman and I H Krakoff
Drug Metabolism and Disposition May 1, 1986, 14 (3) 349-352;

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Abstract

Clinical pharmacology of polyethylene glycol-L-asparaginase.

D H Ho, N S Brown, A Yen, R Holmes, M Keating, A Abuchowski, R A Newman and I H Krakoff
Drug Metabolism and Disposition May 1, 1986, 14 (3) 349-352;
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