Comparative pharmacokinetics and bioavailability of two oral formulations of thiocolchicoside, a GABA-mimetic muscle relaxant drug, in normal volunteers

Perucca, Emilio; Poitou, P; Pifferi, G.

doi:10.1007/bf03190249

Cited by 11 publications

(9 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In conclusion, our results confirm the report of Sutherland et al [7] showing that the previously published data on the metabolism and PK of TCC are incorrect, these results having been obtained using either a nonspecific RIA [4,5] or a GC-MS method that only measures the aglycone moiety [6]. Moreover, even the specific LC/MS-MS method, which quantifies the TCC and the aglycone, did not assay all the pharmacologically active metabolic entities [7,11].…”

Section: O N C L U S I O Nmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…However, as Sutherland et al. [7] recently pointed out, the analytical methods used in these studies, namely, radioimmunoassay (RIA) [4,5] and gas chromatography coupled with mass spectrometry (MS) after enzymatic hydrolysis of TCC to its aglycone, 3‐demethylthiocolchicine [6], do not differentiate the parent compound from potential pharmacologically active or inactive metabolites. Moreover, using a liquid chromatography‐MS‐MS method, Sutherland et al.…”

Section: Introductionmentioning

confidence: 99%

“…It was reported, that after oral administration, TCC is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1 h and with a terminal half-life of 2-6 h [4][5][6]. However, as Sutherland et al [7] recently pointed out, the analytical methods used in these studies, namely, radioimmunoassay (RIA) [4,5] and gas chromatography coupled with mass spectrometry (MS) after enzymatic hydrolysis of TCC to its aglycone, 3-demethylthiocolchicine [6], do not differentiate the parent compound from potential pharmacologically active or inactive metabolites. Moreover, using a liquid chromatography-MS-MS method, Sutherland et al found only traces of the parent drug in plasma of healthy volunteers given 8 mg orally (the recommended therapeutic dose).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

New metabolic and pharmacokinetic characteristics of thiocolchicoside and its active metabolite in healthy humans

Trellu

Filali-Ansary

Francon³

et al. 2004

Fundamemntal Clinical Pharma

View full text Add to dashboard Cite

Thiocolchicoside (TCC) has been prescribed for several years as a muscle relaxant drug, but its pharmacokinetic (PK) profile and metabolism still remain largely unknown. Therefore, we re-investigated its metabolism and PK, and we assessed the muscle relaxant properties of its metabolites. After oral administration of 8 mg (a therapeutic dose) of 14C-labelled TCC to healthy volunteers, we found no detectable TCC in plasma, urine or faeces. On the other hand, the aglycone derivative obtained after de-glycosylation of TCC (M2) was observed and, in addition, we identified, as the major circulating metabolic entity, 3-O-glucuronidated aglycone (M1) obtained after glucuro-conjugation of M2. One hour after oral administration, M1 plus M2 accounted for more than 75% of the circulating total radioactivity. The pharmacological activity of these metabolites was assessed using a rat model, the muscle relaxant activity of M1 was similar to that of TCC whereas M2 was devoid of any activity. Subsequently, to investigate the PK profile of TCC in human PK studies, we developed and validated a specific bioanalytical method that combines liquid chromatography and ultraviolet detection to assay both active entities. After oral administration, TCC was not quantifiable with an lower limit of quantification set at 1 ng/mL, whereas its active metabolite M1 was detected. M1 appeared rapidly in plasma (tmax=1 h) and was eliminated with an apparent terminal half-life of 7.3 h. In contrast, after intramuscular administration both active entities (TCC and M1) were present; TCC was rapidly absorbed (tmax=0.4 h) and eliminated with an apparent terminal half-life of 1.5 h. M1 concentration peaked at 5 h and this metabolite was eliminated with an apparent terminal half-life of 8.6 h. As TCC and M1 present an equipotent pharmacological activity, the relative oral pharmacological bioavailability of TCC vs. intramuscular administration was calculated and represented 25%. Therefore, to correctly investigate the PK and bioequivalence of TCC, the biological samples obtained must be assayed with a bioanalytical method able to specifically analyse TCC and its active metabolite M1.

show abstract

Section: O N C L U S I O Nmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

New metabolic and pharmacokinetic characteristics of thiocolchicoside and its active metabolite in healthy humans

Trellu

Filali-Ansary

Francon³

et al. 2004

Fundamemntal Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…When specific assay methods were used, terminal half-lives following oral and intramuscular administration have been found to be in the orderof5 h (14) and2.7h (15). In a study based on measurements of the aglycone moiety, a mean residence time of 5-6 h was calculated (17).…”

Section: Discussionmentioning

confidence: 99%

Comparative bioavailability and tolerability study of two intramuscular formulations of thiocolchicoside in healthy volunteers

Ferrari

Gatti

Fattore

et al. 2001

Eur. J. Drug Metab. Pharmacokinet.

View full text Add to dashboard Cite

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.

show abstract

The effect of thiocolchicoside on cerebral vasospasm following experimental subarachnoid hemorrhage in the rabbit

et al. 2012

View full text Add to dashboard Cite

show abstract

Comparative pharmacokinetics and bioavailability of two oral formulations of thiocolchicoside, a GABA-mimetic muscle relaxant drug, in normal volunteers

Cited by 11 publications

References 3 publications

New metabolic and pharmacokinetic characteristics of thiocolchicoside and its active metabolite in healthy humans

New metabolic and pharmacokinetic characteristics of thiocolchicoside and its active metabolite in healthy humans

Comparative bioavailability and tolerability study of two intramuscular formulations of thiocolchicoside in healthy volunteers

The effect of thiocolchicoside on cerebral vasospasm following experimental subarachnoid hemorrhage in the rabbit

Contact Info

Product

Resources

About