Single- and repeated-dose pharmacokinetics of intramuscular thiocolchicoside in healthy volunteers

Objective: The aim of this study was to investigate the pharmacokinetics an d the accumulation and stationarity of thiocolchicoside after repeated intr amuscular administration. Method: The pharmacokinetics of thiocolchicoside were studied in 6 healthy male volunteers after one single dose and repeate d intramuscular doses of 4 mg twice a day for seven days. Plasma and urine samples were assayed for thiocolchicoside levels by a radioimmunoassay (RIA .) using a cross-reacting colchicine-specific polyclonal antibody. The phar macokinetic parameters between the first and the last days were compared us ing Student's t-test. Results: Thiocolchicoside pharmacokinetic parameters, calculated after the single dose using non-compartmental analysis, were in good agreement with those obtained in previous studies. Following the repe ated-dose regimen, the terminal half-life was not significantly different ( 2.7 (0.3) h) from that predicted from a single-dose (2.8 (0.2) h). The accu mulation ratio, based on the repeated-dose/single-dose ratio of AUC tau was approximately 1.25. A decrease of CLT/f was found between day 1 (24.1 (5.2 ) l/h) and day 7 (19.9 (3.4) l/h), suggesting that moderate time-related al terations occur in the pharmacokinetics of thiocolchicoside, which may be d ue to a change in its CLNR (CLR was constant) or to the extent of bioavaila bility, explained by enterohepatic recirculation. Conclusion: Serum thiocol chicoside concentrations accumulated to steady-state when the drug was give n twice a day for seven days and the pharmacokinetics were modified. But no adjustments of dose or dosing interval were necessary because the accumula tion did not lead to marked change in the plasma levels.