신규 항암성 화합물 아크리플라빈과 구아노신 복합체를 흰쥐에 근육주사시 아크리플라빈의 체내분포

Distribution of Acriflavine in Rats Following Intramuscular Administration of a Mixture of Acriflavine and Guanosine, a Potential Antitumor Agent

A 1:1 mixture of acriflavine (ACF; CAS 8063-24-9) and guanosine is currently being evaluated as a possible antitumor agent in preclinical studies. Guanosine is known to potentiate the anticancer activity of some compounds. However, the distributions of trypaflavine (TRF) or proflavine (PRF) have not been investigated in mammals. We, therefore, investigated the distribution of TRF and PRF after i.m. administration of the combination mixture (ACF and guanosine) at a does of 30 ㎎/㎏ ACF in rats. To analyze TRF and PRF levels in biological samples, we used an HPLC-based method. The calibration curves for TRF and PRF in the sample were linear over the concenration range of 0.05~200 ㎍/㎖. The intra- and inter-day assay accuracies of this method were within ±15% of norminal values and the precision did not exceed 15% of relative standard diviation. The lower limits of quantitation were 50 ng/㎖ for both TRF and PRF. The distribution of TRF or PRF was determined by 48h after i.m. administraion of the combination mixture at a dose of 30㎎/㎏ ACF. TRF and PRF were distributed as the followeing order; kidney>lung>liver>small intestine>muscle. Of the various tissues, TRF and PRF were mainly distributed to the kidney and lung. The concentrations of TRF or PRF in the tissues 24 h after i.m. administration decreased to undetectable levels. The concentrations of TRF or PRF in the blood cells were comparable to those for the plasma. However, the concentrations of TRF or PRF in the both plasma and blood cells 12h after i.m. administration were not detected. The number of the platelets in the 1㎖ of the blood was calculated to be 0.183×108/㎖ of blood. The PRF concentration in platelets was higher than that of TRF at initial times after i.m. administration of the combination mixture. However, both the TRF and PRF concentrations in the plateles 24h after i.m. administraion of the combination mixture were below the quantifiable limit. In conclusion, the concentrations of TRF or PRF in the various tissues, plasma, blood cells, and plateles decreased to undetectable levels 24h after i.m. administration of the combination mixture at a dose of 30 ㎎/㎏ ACF.