Safety of individual medication of Ma Qian Zi (semen strychni) based upon assessment of therapeutic effects of Guo's therapy against moderate fluorosis of bone.

OBJECTIVE: To assess the safety of individual medication of Guo's Ma Qian Decoction on the basis of effective treatment of fluorosis of bone with Guo's therapy. METHODS: One hundred and fourteen cases of moderate fluorosis of bone were randomly divided into a treatment group (n = 60) and a control group (n = 54) between December 2007 and August 2009 by using the block randomized method and a central random system. At the same time of basic treatment, the patients in the treatment group were orally administrated with Guo's Ma Qian Decoction. The initial dose of Ma Qian Zi (Semen Strychni) was 0.4 g and increased by 0.05 g every two days, with the doses of other drugs unchanged, until the patient had "nux vomica response". For the patients with no "nux vomica response", the dosage was continued to increase and the maximum dosage was not more than 1.2 g/day. The control group was treated with decoction placebo. The changes of strychnine and brucine contents before and after processing and after decoction of Ma Qian Zi (Semen Strychni) were determined with reversed-phase high-performance liquid chromatography, which were controlled within ranges stipulated in the Pharmacopeia; Adverse events were analyzed; Blood strychnine and brucine contents in 10 cases who had taken the drugs were determined. RESULTS: 1) Strychnine (2.125%) and brucine (1.425%) contents before processing of Ma Qian Zi and 1.88% and 1.31% after processing all conformed with the standards of strychnine (1.2-2.2%) and brucine (no less than 0.8%) stipulated in the Pharmacopeia. When the maximum dosage of Ma Qian Zi was 1.2 g/day, strychnine in the decoction was 11.17 mg and brucine was 7.44 mg, which all conformed with the maximum limited amount (strychnine 13.32 and brucine no less than 4.8 mg) stipulated in the Pharmacopeia. 2) Eight cases had "nux vomica response" in the treatment group and one case in the control group, with a significant difference between the two groups (P < 0.05). 3) Altogether 18 cases had adverse events, with an incidence rate of 15.38% (8 cases) in the treatment group and 18.52% (10 cases) in the control group, with no difference between the two groups (P > 0.05); Among them, 10 cases (8.77%) with the adverse event were not related with therapeutic drugs, with an incidence rate of 6.67% (4 cases) in the treatment and 11.11% (6 cases) in the control group, with no significant difference between the two groups (P > 0.05). Seven cases had suspicious relative adverse events, the risk in the treatment group was 0.658 times of the control group, with no significant difference (P > 0.05), and one case had the toxic reaction of nux-vomica seed. 4) Strychnine and brucine were unable to be detected in the blood in all points of time in the 10 cases who had taken the drugs, indicating that plasma strychnine and brucine contents were lower than the minimum detectable amount (10 ng), and accumulation of strychnine and brucine were not found in blood of the patient during and after administration for 8 weeks. CONCLUSION: The individual medication of Ma Qian Zi (Semen Strychni) in the Guo's therapy has a better safety.