Population pharmacokinetics of pegaptanib sodium (Macugen(®)) in patients with diabetic macular edema

Population pharmacokinetic modeling of pegaptanib was undertaken to determine influence of renal function on apparent clearance. In a randomized, double-masked multicenter trial, intravitreal pegaptanib (0.3, 1.0, or 3.0 mg/eye) was administered in patients with diabetic macular edema every 6 weeks for 12-30 weeks. A one-compartment model with first-order absorption, distribution volume, and clearance was used to characterize the pegaptanib plasma concentration-time profile. In 58 patients, increases in area under the concentration-time curve (AUC) to end of the dosing interval (AUC0-tau) and maximum concentration with repeat doses were 68 years) relative to younger patients due to decreases in creatinine clearance (CRCL), a significant predictor of clearance. Pegaptanib clearance was reduced by 29% when CRCL decreased by 50%. The change in exposure with CRCL (range, 0-190 mL/minute) was < 10-fold with 0.3-3.0 mg doses. While pegaptanib clearance and AUC were significantly influenced by CRCL, the predicted exposure in patients with renal insufficiency or renal failure shows no evidence that a dose adjustment is warranted, given the tenfold margin of safety observed over the dose range of 0.3-3.0 mg.