Pharmacokinetics and penetration into synovial fluid of systemical and electroporation administered sinomenine to rabbits.
Sinomenine is an anti-rheumatoid arthritis (RA) drug derived from the Sinomenium acutum. The major site of RA treatment is within the synovial compartment. However, the pharmacokinetic and penetration into synovial fluid (SF) of sinomenine have not been reported. In our study, the pharmacokinetics and penetration into SF of systemic and electroporation administered sinomenine were investigated by microdialysis incorporated with HPLC-MS/MS. Sinomenine went into plasma and SF more rapidly with higher peak concentration (Cmax ) by intramuscular injection compared with oral administration. The area under the concentration-time graph (AUC0-∞ ) of intramuscularly injected sinomenine was 1,403,294.75 ± 125,534.567 ng min/mL in plasma and 456,116.37 ± 62,648.36 ng min/mL in SF, which were equivalent with those for an oral dose. These results indicated that equal amounts of sinomenine could penetrate into SF by the two administration routes, and the permeation ratios were approximately 1:3. The AUC0-∞ and Cmax were lower with electroporation compared with systemic administration, but the CSF /CPlasma (concentration of sinomenine in SF vs that of plasma) at 90, 120, 150, 180, 240 and 480 min by electroporation was 3- to 10-fold higher relative to systemic administration. This illustrated that sinomenine can be targeted into joints by electroporation, and electroporation is a potential technique for sinomenine's transdermal delivery.
Clinical Pharmacy and Pharmacology Research Institute, The Second Xiangya Hospital, Central South University, Changsha, 410011, People's Republic of China.|Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, 410013, People's Republic of China.
Huan
H
Yan
Clinical Pharmacy and Pharmacology Research Institute, The Second Xiangya Hospital, Central South University, Changsha, 410011, People's Republic of China.
Miao
M
Yan
Clinical Pharmacy and Pharmacology Research Institute, The Second Xiangya Hospital, Central South University, Changsha, 410011, People's Republic of China.
Huan-De
HD
Li
Clinical Pharmacy and Pharmacology Research Institute, The Second Xiangya Hospital, Central South University, Changsha, 410011, People's Republic of China.
Pei
P
Jiang
Clinical Pharmacy and Pharmacology Research Institute, The Second Xiangya Hospital, Central South University, Changsha, 410011, People's Republic of China.
Yang
Y
Deng
Clinical Pharmacy and Pharmacology Research Institute, The Second Xiangya Hospital, Central South University, Changsha, 410011, People's Republic of China.
Hua-Lin
HL
Cai
D000279:Administration, Cutaneous; D000818:Animals; D018274:Electroporation; D007273:Injections, Intramuscular; D016014:Linear Models; D017551:Microdialysis; D009019:Morphinans / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics*; D011817:Rabbits; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013582:Synovial Fluid / Q000737:chemistry* / Q000378:metabolism
D009019:Morphinans; C009271:sinomenine
electroporation; microdialysis; pharmacokinetics; sinomenine; synovial fluid penetration