Systemic toxicity of non-cell corynebacterium parvum (CP) in monkeys.

AIM: Non-cell corynebacterium parvum product (NCPP) is a new preparation of corynebacterium parvum (CP), an immunomodulator that displays anticancer activities. It is prepared by nanotechnology and is intended to minimize the side effects of CP. The aim of the present study was to evaluate the immunogenicity and systemic toxicity of NCPP compared with CP in animals. METHODS: 30 monkeys were randomly divided into 5 groups and given CP (3 mg/monkey), three doses of NCPP (9, 3, 1 mg/monkey) and 0.9% normal saline (NS, 4 ml/monkey) individually by intramuscular injection twice a week for 13 weeks. The immunogenicity and systemic toxicity of NCPP and CP were compared. RESULTS: NCCP and CP caused histopathological changes in the liver, spleen and kidney, but pathologic changes in NCCP-treated groups were slighter than that in the CP group. Only 9 mg/monkey of NCPP caused the similar damage as the CP in intensity. Deposition of immune complexes in the glomerular basement membrane was observed only in the CP group. ELISA detection showed that the anti-CP antibody was at a high level, while the anti-NCPP antibody was at low level and disappeared during the recovery period. CONCLUSION: Our study has led to the view that NCPP is safer than CP.

Role of chlorogenic acid in the toxicity induced by Chinese herbal injections.

Adverse reactions induced by Chinese herbal injections have been frequently reported. However, the precise causes of these adverse reactions are not yet fully understood. The aim of the present study was to determine the role of chlorogenic acid (a ubiquitous component of Chinese herbs) in the toxicity of Chinese herbal injections. Beagle dogs were given chlorogenic acid, Yuxingcao injection, or Qingkailing injection (the latter two both containing chlorogenic acid) by intravenous (i.v.) injection, once a day for 7 or 9 days. The systemic toxicity was evaluated. An additional ultrastructural observation on liver and kidney was performed. Anaphylactoid reactions were obvious in dogs treated with Yuxingcao injection. Varying degrees of ultrastructural changes in liver and kidney were observed in the treated dogs, especially in dogs treated with Chinese herbal injections. Our study has led to the view that chlorogenic acid is not an allergen when administrated by i.v. injection, but liver and kidney injury induced by Chinese herbal injections can be partly attributed to chlorogenic acid.

Effect of route of administration on the pharmacokinetics and toxicokinetics of cinnarizine in dogs.

AIMS: Cinnarizine, a piperazine derivative, is currently used for the treatment of cerebral thrombosis, cerebral arteriosclerosis, subarachnoid hemorrhage and some other diseases. However, it exhibits variable dissolution and low bioavailability after oral administration. Cinnarizine for injection was developed in order to enhance its bioavailability and make the practice more convenient for patients suffering from dysphagia. The aim of the present study was to compare the pharmacokinetics and toxicokinetics of cinnarizine following intravenous and oral administration in dogs and provide scientific basis for the development of cinnarizine for injection. METHODS: Beagle dogs were given single- or multiple-dose of cinnarizine by oral (single-dose: 10mg/kg; multiple-dose: 21.5, 12.9, 4.3mg/kg) and intravenous (single-dose: 10mg/kg; multiple-dose: 10, 6, 2mg/kg) routes. HPLC was applied to detect the plasma concentration of cinnarizine. The pharmacokinetics and toxicokinetics parameters were calculated and compared. RESULTS: The pharmacokinetics of cinnarizine following oral administration in dogs was found to fit the one-compartment mode. That of cinnarizine following intravenous injection in dogs was found to fit the two-compartment model. The relative bioavailability of oral administration was 46.4%. Cinnarizine cumulated significantly in dogs when 10mg/kg cinnarizine was injected repeatedly. Multiple-dose of cinnarizine over 6mg/kg induced reversible kidney injury in dogs. CONCLUSION: The present study indicates that pharmacokinetics and toxicokinetics properties of cinnarizine for injection show advantages over the oral preparation. But caution should be taken with the cumulative action when cinnarizine is injected and the dose of cinnarizine should be lower than 6mg/kg.