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• W2102674639 abstract "Modification of recombinant human interleukin-2 (IL-2) with polyethylene glycol (PEG-IL-2) decreases clearance and might favor absorption into the lymphatics, due to its increased molecular weight. In the present study, we compared the plasma and lymph concentrations of IL-2 and PEG-IL-2 in Yorkshire pigs. The IL-2 regimens were i.v. bolus (0.1-1.6 x 10(6) I.U., MIU/kg), 15-min i.v. infusion (0.1 MIU/kg), or s.c. bolus (0.1-3.0 MIU/kg). The PEG-IL-2 doses were 15-min i.v. infusion (0.01 MIU/kg) or s.c. bolus (0.01-0. 10 MIU/kg). Lymph and plasma data were analyzed using noncompartmental methods and NONMEM. Bioavailability of IL-2 was route- and dose-dependent. Bioavailability of i.v. bolus doses of >/=0.16 MIU/kg was complete but only 39% at 0.1 MIU/kg. For the infusion and s.c. doses, bioavailability was 28 and 42%, respectively. Noncompartmental and NONMEM estimates of clearance and volume of distribution at steady state agreed: 300 ml/h/kg and 570 ml/kg, respectively, for IL-2. The ratio of the area under the curve in lymph and plasma increased from 0.67 to 3.4 when comparing i.v. and s.c. routes, and the s.c. delivery advantage (ratio of dose-normalized ratio of the area under the curve in lymph after s.c. and i.v. administration) was 6.6 to 16. For PEG-IL-2, bioavailability was 100%, clearance was 5.9 ml/h/kg, and volume of distribution at steady state was 370 ml/kg. The ratio of the area under the curve in lymph and plasma increased from 0.33 (i.v.) to 1. 2 (s.c.), and the s.c. delivery advantage was 3.8. Subcutaneous dosing would be favored over i.v. dosing, and IL-2 would be favored over PEG-IL-2 to maximize lymph and minimize plasma exposure. Because IL-2 efficacy may be related to lymph concentrations, dosing regimens can now be designed to test this hypothesis." @default.
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• W2102674639 date "2000-04-01" @default.
• W2102674639 modified "2023-10-02" @default.
• W2102674639 title "Plasma and lymph pharmacokinetics of recombinant human interleukin-2 and polyethylene glycol-modified interleukin-2 in pigs." @default.
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