Comparative bioavailability and tolerability study of two intramuscular formulations of thiocolchicoside in healthy volunteers.
The comparative bioavailability and tolerability of two intramuscular fomulations of thiocolchicoside (test, Thiocolchicoside, 4 mg ampoules, Dompé S.p.A.; reference, Muscoril, 4 mg ampoules, Inverni della Beffa S.p.A.) were investigated in twelve healthy volunteers according to a single dose (4 mg), cross-over, randomized design. Plasma thiocolchicoside concentrations were determined by using a validated specific HPLC/MS assay and local tolerability was investigated by assessing subjective pain intensity on a visual analogue scale (VAS), reddening at the injection site, and plasma creatinine phosphokinase (CPK) levels. Pharmacokinetic parameters after administration of the test formulation were similar to those observed after administration of the reference (Tmax 0.50 (0.25-1.00) vs 0.50 (0.25-1.00), median and range; Cmax 115.5 +/- 26.6 vs 113.2 +/- 40.4 ng/ml; AUC 291.6 +/- 77.7 vs 283.3 +/- 98.9 ng.h/ml, means +/- SD). Relative bioavailability (F) was 1.05 +/- 0.13. Statistical comparison of pain intensity, CPK levels and occurrence of redness at the injection site did not show statistically significant differences between formulations. It is concluded that the investigated test formulation is bioequivalent and equally well tolerated as the marketed reference formulation.
Ferrari
M P
MP
Dompé S.p.A., Medical Department, Milano, Italy.
Gatti
G
G
Fattore
C
C
Fedele
G
G
Novellini
R
R
D000328:Adult; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003078:Colchicine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D011897:Random Allocation; D012016:Reference Values
D003078:Colchicine; C004280:thiocolchicoside