In this article, we will discuss Aldesleukin (Clinical Pharmacology). So, let’s get started.
Clinical Pharmacology
Aldesleukin has been shown to possess the biological activities of human native
interleukin-2 In vitro studies performed on human cell lines demonstrate the
immunoregulatory properties of Proleukin, including: a) enhancement of lymphocyte
mitogenesis and stimulation of long-term growth of human interleukin-2 dependent cell lines; b) enhancement of lymphocyte cytotoxicity; c) induction of killer cell (lymphokine-activated (LAK) and natural (NK)) activity; and d) induction of interferon-gamma production. The in vivo administration of Aldesleukin in animals and humans produces multiple immunological effects in a dose dependent manner. These effects include activation of cellular immunity with profound lymphocytosis, eosinophilia, and thrombocytopenia, and the production of cytokines including tumor necrosis factor, IL-1 and gamma interferon. In vivo experiments in murine tumor models have shown inhibition of tumor growth.The exact mechanism by which Proleukin mediates its antitumor activity in animals and humans is unknown.
Pharmacokinetics
Aldesleukin exists as biologically active, non-covalently bound microaggregates with an average size of 27 recombinant interleukin-2 molecules. The solubilizing agent, sodium dodecyl sulfate, may have an effect on the kinetic properties of this product. The pharmacokinetic profile of Aldesleukin is characterized by high plasma concentrations following a short intravenous infusion, rapid distribution into the extravascular space and elimination from the body by metabolism in the kidneys with little or no bioactive protein excreted in the urine. Studies of intravenous Aldesleukin in sheep and humans indicate that upon completion of infusion, approximately 30% of the administered dose is detectable in plasma. This finding is consistent with studies in rats using radiolabeled Proleukin, which demonstrate a rapid (<1 min) uptake of the majority of the label into the lungs, liver, kidney, and spleen. The serum half-life (T 1/2) curves of Aldesleukin remaining in the plasma are derived from studies done in 52 cancer patients following a 5-minute intravenous infusion. These patients were shown to have a distribution and elimination T 1/2 of 13 and 85 minutes, respectively. Following the initial rapid organ distribution, the primary route of clearance of circulating Aldesleukin is the kidney. In humans and animals, Aldesleukin is cleared from the circulation by both glomerular filtration and peritubular extraction in the kidney. This dual mechanism for delivery of Aldesleukin to the proximal tubule may account for the preservation of clearance in patients with rising serum creatinine values. Greater than 80% of the amount of Aldesleukin distributed to plasma, cleared from the circulation and presented to the kidney is metabolized to amino acids in the cells lining the proximal convoluted tubules. In humans, the mean clearance rate in cancer patients is 268 mL/min. The relatively rapid clearance of Aldesleukin has led to dosage schedules characterized by frequent, short infusions. Observed serum levels are proportional to the dose of Aldesleukin.