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Cetus Corporation, Emeryville, California 94608 [M. K., E. B.]; Department of Internal Medicine, Arizona Cancer Center, Tucson, Arizona 85724 [E. H.]; Department of Cancer Prevention, University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, Texas 77030 [P. M.]; Abteilung fur Hamatologie, Johannes Gutenberg-Universitat, Langenbeckstrasse 1, 6500 Mainz 1, Federal Republic of Germany [R. M.]; Department of Medicine, Health Sciences Center, University of Oklahoma, Oklahoma City, Oklahoma 73190 [G. M.]; and Hematology/Lymphoma and Clinical Immunology Services, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 [J. K.]
This report summarizes the pharmacokinetics in humans of recombinant interleukin 2 (IL-2) given as an i.v. bolus, i.v. or i.p. infusion, and i.m. or s.c. injection. Immediately after an i.v. bolus the serum IL-2 level equals the dose divided by the plasma volume, in a typical human 650 units/ml for a dose of 106 units/m2. The level initially decreases with a half-life of 12.9 min, followed by a slower phase with a half-life of 85 min out to 4 h after the bolus. The median steady state level during an i.v. infusion of 106 units/m2 over 6 h is 41 units/ml. A clearance rate of approximately 120 ml/min is obtained from either the i.v. bolus or infusion data and is consistent with the renal filtration being the major route of clearance. Serum levels remain fairly constant for about 8 h after s.c. or i.m. injection but are approximately 2% of the level seen immediately after an i.v. bolus. The area under the time-concentration curve suggests that about 30% of the IL-2 activity is transported from the site of an i.m. injection to the blood. After i.p. infusion IL-2 is only slowly transported to the blood. The median serum IL-2 levels are 430-fold lower than levels in the i.p. fluid and decrease with a median half-life of 6.3 h.
1 To whom requests for reprints should be addressed.
2 Present address: Sterling Drug Inc., Building 9, Great Valley Parkway, Malvern, PA 19355.
Received 8/17/89.
Revised 12/12/89.
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