Single-dose pharmacokinetics and tolerability of alendronate 35- and 70-milligram tablets in children and adolescents with osteogenesis imperfecta type I.
BACKGROUND
Alendronate (ALN) is a bisphosphonate compound that can be administered orally and has potential use in pediatric osteoporotic conditions.


OBJECTIVE
The objective was to evaluate the pharmacokinetics and single-dose tolerability of ALN in children with osteogenesis imperfecta.


METHODS
ALN was administered iv and orally in a two-period, randomized crossover study, with doses separated by a 2-wk washout and follow-up carried out within 2 wk after the last ALN dose.


METHODS
The study was conducted at the pediatric metabolic bone research unit at the Shriners Hospital for Children, Montréal, Canada.


METHODS
Twenty-four children (aged 4-16 yr; eight girls) with osteogenesis imperfecta type I participated.


METHODS
All patients received iv ALN at a dose of 125 mug. In addition, patients weighing less than 40 kg received an oral dose of ALN 35 mg, whereas those weighing 40 kg or more received ALN 70 mg orally.


METHODS
Total urinary excretion and oral bioavailability of ALN, blood and urine safety parameters, and adverse events were the main outcome measures.


RESULTS
The total urinary excretion of ALN after the iv dose was similar for both weight groups. The mean oral bioavailability (95% confidence interval) was 0.43% (0.28, 0.64%) for patients weighing less than 40 kg and 0.56% (0.36, 0.87%) for patients weighing 40 kg or more. Eighteen patients reported a total of 44 clinical adverse experiences, none of which were serious. The most common adverse experiences were mild to moderate headache (n = 7), nausea (n = 7), fever (n = 5), and abdominal pain (n = 6). Eighty percent of the adverse experiences (35 of 44) occurred within 48 h of medication administration, 91% (40 of 44) lasted less than 24 h, and 84% (37 of 44) were reported after oral dosing. Laboratory safety monitoring revealed a marginal decrease in absolute lymphocyte count and serum alkaline phosphatase after the study compared with baseline for both weight categories.


CONCLUSIONS
The mean oral bioavailability of 35- and 70-mg ALN tablets was less than 0.6%, comparable to adult studies. Adverse experiences from single-dose ALN were minor, and the drug was generally well-tolerated.
Ward
L M
LM
Genetics Unit, Shriners Hospital for Children, and McGill University, 1529 Cedar Avenue, Montréal, Québec, Canada H3G 1A6.
Denker
A E
AE
Porras
A
A
Shugarts
S
S
Kline
W
W
Travers
R
R
Mao
C
C
Rauch
F
F
Maes
A
A
Larson
P
P
Deutsch
P
P
Glorieux
F H
FH
D000293:Adolescent; D019386:Alendronate / Q000009:adverse effects / Q000493:pharmacokinetics*; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D010013:Osteogenesis Imperfecta / Q000188:drug therapy*; D013607:Tablets
D013607:Tablets; D019386:Alendronate