A Single-Dose Bioavailability Study of Pamidronate Disodium after Oral Administration as Encapsulated Enteric-Coated Pellets, Enteric-Coated Tablets, and a Solution to Patients with Postmenopausal Osteoporosis.

: This was a pilot, single-center, single-dose, open-label, randomized three-way crossover study comparing the relative bioavailability of pamidronate disodium after oral doses of the drug administered as four capsules, each containing 75 mg enteric-coated pellets, two 150-mg enteric-coated tablets and 300 mg in solution (reference standard) in patients with postmenopausal osteoporosis. Results from seven patients are reported; five subjects completed all three phases of the study---one received solution and pellets, and another one received pellets and tablets. The onset of urinary excretion (an indicator of relative onset of oral absorption) of pamidronate disodium occurred in the first 2 h in all (except one) patients for solution and pellets, whereas the onset of urinary excretion for the tablets was prolonged and more variable. The extent of absorption was estimated in terms of percent of administered dose excreted in urine up to 72 h after dosing. The extend of absorption was highest after the pellets (mean plus minus S.D., 0.37 plus minus 0.27%), followed by the solution (0.20 plus minus 0.16%). The extent of absorption after the tablets (0.09 plus minus 0.10%) was the lowest and most variable. The poorer and more variable bioavailability of the tablets may be explained by the longer and more variable residence time of the tablets in the stomach.