OBJECTIVE To evaluate the bioequivalence of domestic cilnidipine capsules and commercially available cilnidipine tablets in healthy Chinese volunteers. METHODS Twenty healthy male Chinese volunteers were enrolled and orally administrated 10 mg cilnidipine capsules or tablets randomly and the concentrations of cilnidipine in plasma were determined by HPLC-MS/MS. RESULTS The pharmacokinetic parameters of two cilnidipine productions were as following： ρmax（11.08±4.42）and（2.94±3.44）μg·L-1， tmax（1.30±0.56）and（2.21±1.25）h， t1/2 (3.99±1.90) and (4.55±1.75) h，AUC0-16 h (35.28±14.63) and (13.22±12.44) μg·h·L-1，AUC0-∞(38.05±16.49) and (15.43±13.59) μg·h·L-1，respectively. There were significant differences in ρmax, tmax, AUC0-t and AUC0-∞ between the two formulations. CONCLUSION The domestic cilnidipine capsules were not bioequivalent to the marketed cilnidipine tablets in China.
Key words
cilnidipine /
pharmacokinetics /
bioequivalence
{{custom_keyword}} /
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
References
［1］ ISHII M. A multicenter double-blind comparision study of FRC-8653(cilnidipine) and nicadipine-retard in patients with essential hypertension［J］. Jpn Pharmacol Ther，1993，21(1)：59-97.
［2］ TOMINAGA M， OHYA Y， TSUKASHIMA A， et al.Ambulatory blood pressure monitoring in patients with essential hypertension treated with a new calcium antagonist， cilnidipine ［J］. Cardiovasc Drugs Ther， 1997，11(1)：43-48.
［3］ SARUTA T. Current status of calcium antagonists in Japan ［J］. Am J Cardiol，1998， 82(9B)：32-34.
［4］ KATO K， WAKAMORI M， MORI Y， et al. Inhibitory effects of cilnidipine on peripheral and brain N-type Ca2+ channels expressed in BHK cells ［J］. Neuropharmacology， 2002，42(8)：1099-1108.
［5］ MINAMI J， ISHIMITSU T， KAWANO Y， et al. Comparison of 24 h blood pressure， heart rate， and autonomic nerve activity in hypertensive patients treated with cilnidipine or nifedipine ［J］. J Cardiovasc Pharmacol，1998， 32(2)：331-336.
［6］ JING S, SUN N L, WANG H Y, et al. Efficacy and safety of cilnidipine for mild and moderate primary hypertension［J］. Chin J New Drugs（中国新药杂志）， 2005，14(4)：473-475.
［7］ ZHAO X L, ZHANG H, HU D Y. Efficacy and safety of cilnidipine tablet in the treatment of mild to moderate hypertension［J］. Chin J Clin Pharmacol（中国临床药理学杂志），2005，21（1）：8-10.
［8］ MA S P, GUO X M, LI C R, et al. Efficacy and safetay of cilnicipine in treatming mild to moderate essential hypertension［J］. Chin J New Drugs Clin Rem（中国新药与临床杂志），2004，23（12）：873-875.
［9］ MATSUZAWA Y， OKIKAWA I， OZAKI M， et al. Absorption， distribution and excretion of 2-methoxyethyl-3-phenyl- 2(E)- propenyl 1，4- dihydro- 2， 6-dimethyl-4-(3-nitrophenyl)-3，5- pyridinedicarboxylate (FRC-8653) after single oral administration to dogs ［J］. Jpn Pharmcol Ther，1992， 20 (10)：131-141.
［10］ MATSUZAWA Y， OKIKAWA I， GONSHO A， et al. Absorption， distribution and excretion of 2-methoxyethyl-3-phenyl- 2(E)- propenyl 1，4- dihydro- 2， 6- dimethyl -4(3-nitrophenyl)-3，5- pyridinedicarboxylate (FRC-8653) after single oral administration to rats ［J］. Jpn Pharmcol Ther， 1992，20 (10)：111-129.
［11］ LEE H W， SEO J H， LEE H S， et al. Development of a liquid chromatography/negative-ion electrospray tandem mass spectrometry assay for the determination of cilnidipine in human plasma and its application to a bioequivalence study ［J］.J Chromatogr B， 2008，862（1-2）：246-251.
［12］ ZHANG X H， ZHAI S D， ZHAO R S， et al. Determination of cilnidipine， a new calcium antagonist， in human plasma using high performance liquid chromatography with tandem mass spectrometric detection ［J］. Anal Chim Acta， 2007，600（1-2）：142-146.
［13］ Ch.P (2000) Vol Ⅱ （中国药典 2000年版.二部）［S］. 2000：Appendix 75.
{{custom_fnGroup.title_en}}
Footnotes
{{custom_fn.content}}
PDF(723 KB)
