ABSTRACT
Objective: To study the pharmacokinetics and tissue distribution of procesed Strychni Semen in rats after multiple administration at clinical dose. Methods: The rats were given procesed Strychni Semen by intragastric administration for single and several times. The plasma concentrations of brucine and strychnine in plasma and tissues of rats were determined by UPLC-Q-Orbitrap HRMS method, and the organizational distribution differences were compared to explore whether there was accumulation in the body. Results: After single intragastric administration of procesed Strychni Semen, the main pharmacokinetic parameters of brucine and strychnine were as follow: t1/2 was 10.59 and 8.39 h, tmax was 0.77 and 0.64 h, t1/2Ka was 5.38 and 2.63 h, Cmax was 2.97 and 10.83 ng/L, AUC0-t was 87.36 and 172.24 ng∙h/L, CL/F was 40 637.08 and 38 370.26 L/(h∙kg); Brucine and strychnine in processed Strychni Semen reached a steady state after 3 d of administration in rats. After the last administration, the main pharmacokinetic parameters of brucine and strychnine in rats were as follow: t1/2 was 7.07 and 4.75 h, tmax was 0.48 and 0.46 h, t1/2Ka was 3.23 and 1.09 h, Cmax is 5.77 and 34.83 ng/L, AUC0-t was 32.80 and 107.86 ng∙h/L, and CL/F was 75 920.52 and 43 871.54 L/(h∙kg). Compared with the single administration, the content of brucine and strychnine in the liver and kidney tissues was significantly reduced after multiple administrations, and there was no significant change in other tissues. Conclusion: The pharmacokinetics of brucine and strychnine in healthy rats is consistent with one-compartment model. Both of them have the pharmacokinetic characteristics of fast absorption in rats. After 3 d of administration, the serum concentrations of brucine and strychnine reached steady state, and the blood concentration was increased continuously with the increase of administration times. The content of each tissue did not increase after single and multiple administrations. It is suggested that long-term administration of brucine and strychnine will not cause the superposition of the concentration of brucine and strychnine in the blood of rats, which may lead to the occurrence of poisoning.
ABSTRACT
OBJECTIVE:To study the safety of percutaneous administration of Hongzhi gutong cataplasm. METHODS:Rab-bits were taken for single dose in complete skin irritation test(n=4),single dose in damaged skin irritation test(n=4)and multi-ple doses in complete skin irritation test(n=4). The left and right sides of the skin respectively paste 3 cm×3 cm blank matrix and Hongzhi gutong cataplasm for 24 h(calculated by crude drug of 0.14 g). After removing tape 1,24,48,72 h,the erythema and edema in hair removal site of rabbits in the former 2 tests were observed;after 24 h of administration,the rabbits in the last group were administrated again after exposing the administration area for 1 h,repeated 3 times,the erythema and edema in hair removal site after removing tape the first,second time and 1,24,48,72 h in the third time were respectively observed. RESULTS:In the 3 experiments,the scores of erythema and edema of all rabbits were 0,and skin irritation was evaluated as no irritation. CONCLU-SIONS:Hongzhi gutong cataplasm has no skin irritation in rabbits.
ABSTRACT
OBJETIVO: Avaliação comparativa da freqüência de hipoglicemia severa após mudança da terapia com múltiplas doses de insulina (MDI) para bomba de insulina subcutânea (BIISC). PACIENTES E MÉTODOS: Sete pacientes DM1, idade Mi = 14 anos e tempo médio de diabetes de 8 anos, comparados de acordo com a incidência de hipoglicemia, a dose total de insulina (U/Kg/d), IMC (Kg/m²) e HbA1c (vn: 3,5-6,7 por cento) 1 ano antes e 1 ano após a transferência de terapêutica. Houve redução significativa dos episódios de hipoglicemia severa (1,3 episódio/paciente/ano para zero episódio/paciente/ano; p = 0,04), na dose total diária de insulina (1,33 ± 0,26 U/Kg/dia para 0,87 ± 0,17 U/kg/dia; p = 0,04) e na HbA1c (8,7 ± 0,7 por cento para 7,8 ± 0,9 por cento; p = 0,05 com BIISC). Concluímos que a BIISC é eficaz e segura na redução de hipoglicemia severa em um subgrupo de pacientes DM1 com MDI. Entretanto, os resultados obtidos precisam ser reproduzidos em centros semelhantes e estudos de custo são necessários para que a sua viabilidade seja confirmada e aplicada nos sistemas públicos de saúde, que correspondem à maioria no nosso país.
OBJECTIVE: We compared the incidence of severe hypoglycemia episodes with therapy with multiple doses of insulin (MDI) and after changing to pump (CSII). PATIENTS AND METHODS: 7 T1DM patients with 14 years median and median duration of diabetes of 8 years. We analyzed insulin requirement (U/kg/day), BMI (Kg/m²), HbA1c (normal range: 3.5-6.7 percent) one year before and one year after changing therapy. The severe hypoglycemia episodes decreased from 1.3 to 0 episodes/patient/year; p = 0.00). The insulin requirement decreased from 1.33 ± 0.26 U/Kg/day to 0.87 ± 0.17 U/kg/day; p = 0.04 and HbA1c decreased from 8.7 ± 0.7 percent to 7.8 ± 0.9 percent; p = 0.05. CONCLUSION: CSII is efficient in decreasing severe hypoglycemia in a subgroup of T1DM using MDI also in Public Health Care System (PHCS) conditions. However, these finding should be reproduced by other Diabetes Care centers and cost studies are necessary to confirm the viability and possibility of this therapy, when necessary, to T1DM patients, which correspond to the majority of these individuals in our country, seeing in the PHCS.