Clinic Pharmacokinetic Profiles of Huperzine A Following Transdermal Administration to Healthy Human Volunteers

Abstract

To support the rationale behind the development of the huperzine A patches and its pharmacological effects in clinical therapy, an LC-MS-MS method was developed and validated for determination of huperzine A in human plasma and then applied to the clinic pharmacokinetics study on transdermal patches of huperzine A. After a simple liquid-liquid extraction with ethyl acetate, analytes were separated on a C18 column with isocratic elution. The detection of analytes was performed on a tandem mass system equipped with an electrospray ionization source in positive mode using multiple-reaction monitoring. The MS-MS ion transitions monitored were m/z 243.2?210.1 for huperzine A and m/z 248.1?128.0 for tinidazole (internal standard). Method validation and sample analysis were performed according to FDA guidelines and the results met the acceptance criteria. The pharmacokinetic profiles of huperzine A following single transdermal administration of 8, 10 and 12 mg huperzine A to healthy human volunteers were depicted using the established method. The results showed that the pharmacokinetic behavior of huperzine A in vivo was present as linear dynamic characteristics with much longer T max , lower C max , and relatively constant plasma concentration. No gender difference and obvious adverse effects were observed from all three groups in our study. Our study indicated that the huperzine A transdermal patches could provide continuous drug delivery over 120 h with favorable tolerability. This may allow patients to obtain optimal plasma concentrations of drugs and to benefit from a longer duration of treatment.

Dissolving microneedles for transdermal delivery of huperzine A for the treatment of Alzheimer's disease

“…One common disadvantage of the traditional transdermal system is the low bioavailability. Therefore, sufficient medicine is required as the penetration force, and a large amount of the medicine still remains after wearing (Ye et al., 2008 ; Wu et al., 2011 ; Amjadi et al., 2018 ; Lee & Prausnitz, 2018 ). Results in this study indicated that DMNP can prolong the elimination of t 1/2 and enlarge the area under the curve (AUC), presenting a higher relative bioavailability value than that of oral administration.…”