Pharmacokinetic Study on Testosterone Gel Enhanced by N-Trimethyl Chitosan in Rabbits
HE Wen1，ZHANG Mian2，HE Ping-ping2
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1．Department of Pharmacy，Renmin Hospital，Wuhan University，Wuhan 430060，China；2.Department of Pharmacy，Wuhan University，Wuhan 430072，China
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Received
Published
2006-01-09
2007-03-05
Issue Date
2007-03-05
Abstract
OBJECTIVE To study the pharmacokinetics of testosterone gel enhanced by N-trimethyl chitosan(TMC) in rabbits and to estimate the penetration enhancement effect of TMC.METHODS Two kinds of TMC with different degree of quaternization,i.e.TMC40 and TMC60,were synthesized by a two-step method using chitosan and methyl-iodide.The degree of quaternization of TMC was determined by 1H-NMR.Four kinds of gels were prepared using testoterone as model drug.Azone(2%) were used as penetration enhancer in the positive control group.No enhancer was used in the blank control.TMC40(5%) and TMC60(5%) was used as penetration enhancer respectively in the other two groups.Plasma concentrations of testosterone were determined using RP-HPLC method.Pharmacokinetic parameters were calculated to estimate the influence of TMC on penetration enhancement.RESULTS The degree of quaternization of TMC40 and TMC60 were 38.8% and 67.2%,respectively.The main pharmacokinetic parameters were compared by t test.The pharmacokinetic parameters of TMC60 showed significant differences compared with both Azone and the blank control(P<0.05),as well as TMC40 compared with the blank control (P<0.05).However,no significant difference was found between TMC40 and Azone group except the parameter Ka(P>0.05).CONCLUSION TMC60 has significant penetration enhancement on the transdermal delivery of testosterone gel.The penetration enhancement of TMC40 is stronger than that of the blank control significantly,however the difference is not significant compared with Azone(2%).
HE Wen;ZHNG Min;HE Ping-ping.
Pharmacokinetic Study on Testosterone Gel Enhanced by N-Trimethyl Chitosan in Rabbits [J]. Chinese Pharmaceutical Journal, 2007, 42(05): 378-381
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