Study on Relative Bioavailability of Nicergoline Capsules in Healthy Volunteers by the Determination of MMDL

ZHOU Yn-in;TIN Jun;RN Li-ling;ZUO Ying;HU Go-yun;DING Jin-song

Chinese Pharmaceutical Journal ›› 2008, Vol. 43 ›› Issue (22) : 1740-1743.

Chinese Pharmaceutical Journal ›› 2008, Vol. 43 ›› Issue (22) : 1740-1743.
论著

Study on Relative Bioavailability of Nicergoline Capsules in Healthy Volunteers by the Determination of MMDL

  • ZHOU Yan-bin,TIAN Juan,RAN Li-ling,ZUO Ying,HU Gao-yun,DING Jin-song
Author information +
History +

Abstract

OBJECTIVE To establish a HPLC method for the determination of MMDL(1-methyl-10α-methoxy-9,10-dihydrolysergol) in plasma and study the relative bioavailability of domestic and imported nicergoline capsules.METHODS MMDL were extracted from plasma sample with dichloromethane(including 10% isopropanol) and separated on a Diamonsil C18 column(4.6 mm×200 mm,5 μm).The mobile phase consisted of acetonitrile-20 mmol·L-1 potassium dihydrogen phosphate(22∶78),the flow rate was 1 mL·min-1,and methocarbamol was used as the internal standard.A single dose of 60 mg of domestic or imported capsules was given to 18 healthy volunteers in a randomized crossover study.MMDL concentrations in plasma was determined by the developed HPLC method,and then the pharmacokinetics and bioavailability were studied.RESULTS MMDL was separated well from other metabolites and endogenous substance,the standard curve was linear(r=0.999 7) within the range of 1.7 to 207 μg·L-1 for MMDL.The main parameters for MMDL were as follows: ρmax(97.9±54.6) and(103.0±60.5) μg·L-1,tmax(1.2 ±0.4)and(1.2±0.4)h,t1/2(3.7±2.6)and(4.0±3.0)h,AUC0→12 h(283.7±218.4) and(305.3±244.6)μg·h·L-1 respectively.The relative bioavailability of domestic to imported capsules was(93.8±6.4)%.CONCLUSION The established HPLC method was accuracy and sensitive for assay of plasma MMDL concentration.And the concentrations of MMDL in plasma were suitable for the bioavailability evaluation of nicergoline capsules.The results of statistics showed there were no significant differences between two preparations,and bioequivalence was observed.

Key words

1-methyl-10α-methoxy-9 / 10-dihydrolysergol / nicergoline / HPLC / bioavailability

Cite this article

Download Citations
ZHOU Yn-in;TIN Jun;RN Li-ling;ZUO Ying;HU Go-yun;DING Jin-song. Study on Relative Bioavailability of Nicergoline Capsules in Healthy Volunteers by the Determination of MMDL [J]. Chinese Pharmaceutical Journal, 2008, 43(22): 1740-1743

References

[1] SIOUF A,SANDRENAN N,GODBILLON J,et al. Determination of 10α-methoxy-9,10-dihydroly- sergol,a nicergoline metabolite,in human urine by high performance liquid chromatography[J] . Biomedi Chromatogr,1992,6(1):9-11. [2] YU J,DU C B. Determination of 10α-methoxy-9,10-dihydrol- ysergol (a Nicergoline Metabolite) in human plasma by HPLC[J] . Chin J Pharm Anal(药物分析杂志),1998,18(2):78-80. [3] BANNO K,HORIMOTO S. Separation and quantitation of nicerg- oline and related substances by high-performance liquid chromatography- atmospheric pressure ionization mass spectrometry[J] . Chromatograph,1991,31(1/2):50-54. [4] EZAN E,DELESTRE F,LEGENDRE S,et al. Immunoassays for the detection of nicergoline and its metabolites in human plasma[J] . J Pharm Biomed Anal,2001,25(1):123-130. [5] BOTTIGER Y,DOSTERT P,STROLIN B M,et al. Involvement of CYP2D6 but not CYP2C19 in nicergoline metabolism in humans[J] . Br J Clin Pharmacol,1996,42(6):707-711.

55

Accesses

0

Citation

Detail

Sections
Recommended

/