Studies of the oral bioavailability of alendronate.
Clinical studies were performed to examine the oral bioavailability of alendronate (4-amino-1-hydroxy-butylidene-1,1-bisphosphonate monosodium). All studies, with the exception of one performed in men, involved postmenopausal women. Short-term (24 to 36 hours) urinary recovery of alendronate after an intravenous dose of 125 to 250 micrograms averaged about 40% in both men and women. In women, oral bioavailability of alendronate was independent of dose (5 to 80 mg) and averaged (90% confidence interval) 0.76% (0.58, 0.98) when taken with water in the fasting state, followed by a meal 2 hours later. Bioavailability was similar in men [0.59%, (0.43, 0.81)]. Taking alendronate either 60 or 30 minutes before a standardized breakfast reduced bioavailability by 40% relative to the 2-hour wait. Taking alendronate either concurrently with or 2 hours after breakfast drastically (> 85%) impaired availability. Black coffee or orange juice alone, when taken with the drug, also reduced bioavailability (approximately 60%). Increasing gastric pH, by infusion of ranitidine, was associated with a doubling of alendronate bioavailability. A practical dosing recommendation, derived from these findings and reflective of the long-term nature of therapy for a disease such as osteoporosis, is that patients take the drug with water after an overnight fast and at least 30 minutes before any other food or beverage.
Gertz
B J
BJ
Merck Research Laboratories, Rahway, NJ 07065-0914, USA.
Holland
S D
SD
Kline
W F
WF
Matuszewski
B K
BK
Freeman
A
A
Quan
H
H
Lasseter
K C
KC
Mucklow
J C
JC
Porras
A G
AG
D000126:Achlorhydria / Q000139:chemically induced / Q000378:metabolism; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D019386:Alendronate; D000704:Analysis of Variance; D001628:Beverages; D001682:Biological Availability; D002118:Calcium / Q000494:pharmacology; D018592:Cross-Over Studies; D004164:Diphosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005502:Food; D005753:Gastric Mucosa / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy; D011899:Ranitidine / Q000494:pharmacology
D004164:Diphosphonates; D006635:Histamine H2 Antagonists; D011899:Ranitidine; D002118:Calcium; D019386:Alendronate