Pharmacokinetic evaluation of pamidronate after oral administration: a study on dose proportionality, absolute bioavailability, and effect of repeated administration.

To evaluate dose proportionality and absolute bioavailability of a new enteric-coated pellet formulation of pamidronate disodium (AREDIA), nine females (aged 52-66 years) were given three different single peroral doses of pamidronate disodium (75, 150, and 300 mg) and an i.v. infusion of 15 mg over 30 minutes at constant infusion rate. Repeated peroral doses (75 and 150 mg) were administered to 12 females (aged 51-70 years) for 10 consecutive days. Urinary excretion of pamidronate after peroral and i.v. administration was used for estimation of pamidronate absorption. Renal excretion of pamidronate ranged from 0.01% to 0.35% of dose, with mean values of 0.11, 0.16, and 0.18% for 75, 150, and 300 mg, respectively. After i.v. infusion, the renal excretion of pamidronate was 26-53% of the dose, lower than for other bisphosphonates. The absolute bioavailability was 0.31% (range 0.08-0.7%) after 75 mg, 0.43% (0.01-1.20%) after the 150-mg dose, and 0.48% (0.07-1.06%) following 300 mg of pamidronate disodium. Urinary excretion after the 10th intake showed a significant increase (difference 0.07% (range -0.003-0.29%), P < 0.02) when compared with the first dose. In conclusion, intestinal uptake of pamidronate was low with high intraindividual variation, like other bisphosphonates.