Pharmacokinetic and tolerability of i.m. disodium clodronate 200 mg/lidocaine 1%,
given twice monthly, in comparison with i.m. disodium clodronate 100 mg/lidocaine
1%, given weekly, in healthy postmenopausal female patients.
Author(s): Radicioni M(1), Cremonesi G, Baraldi E, Leuratti C, Mariotti F.
Affiliation(s): Author information:
(1)CROSS Research S.A., Phase 1 Unit, Arzo, Switzerland. e.baraldi@chiesi.com
Publication date & source: 2013, Int J Clin Pharmacol Ther. , 51(4):313-22
BACKGROUND: Clodronate is a bisphosphonate effective in the prevention and
treatment of osteoporosis in postmenopausal women. Non-adherence to
bisphosphonates, however, is a major issue in clinical practice. Simplifying dose
regimens may increase compliance.
OBJECTIVES: To assess bioequivalence between an intramuscular (i.m.) clodronate
200 mg/lidocaine 1% twice-a-month formulation and a clodronate 100 mg/lidocaine
1% weekly formulation in 32 postmenopausal women.
METHODS: In this double-blind, randomized, two-way crossover study, test and
reference formulations were administered in single dose, with a 2-week wash-out
between administrations. The primary endpoint was clodronic acid cumulative
excretion in the first 24 hours after injection (Xu0-24h). Cumulative excretion
in the 72 hours post-dose (Xu0-72h) and maximum excretion rate (Ratemax) were
also evaluated. Bioequivalence was assumed if the 90% confidence intervals (CIs)
of the geometric means ratios of the dose-normalized parameters were within the
80.00 - 125.00% range. Local tolerability was evaluated.
RESULTS: Mean Xu0-24h values were 114.03 ±23.13 mg and 55.22 ±9.73 mg for
clodronate 200 mg and 100 mg. The 90% CIs for dose-normalized Xu0-24h, Xu0-72h
and Ratemax ere 95 -110%, 94 -107% and 95 - 113%. Local tolerability of both
treatments was good. The differences in pain intensity between formulations were
not sigificantly different at most assessment times. Headache was the only
treatment-related adverse event.
CONCLUSIONS: Bioequivalence of the two formulations was confirmed in terms of
dose-normalized rate and amount of clodronic acid excretion. This result,
together with the favorable tolerability of the novel 200 mg formulation,
suggests the possibility of reducing the number of i.m. administrations from
once-a-week to twice-a-month.
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