[Comparative study on hemolytic toxicity of trifluoroacetoprimaquine and primaquine in rabbits].
5-trifluoroacetoprimaquine (M8506) exhibited high effect on tissue schizont of P. cynomolgi and low toxicity in mice, rats and dogs as compared with primaquine (PQ) according to our previous studies. In order to determine their hemolytic toxicity, we dosed rabbits with M8506 and PQ at a dose of 40 mg/kg per day for 4 days, respectively. Blood samples were drawn from the ear vein of the rabbits for determining of the following parameters, ie. methemoglobin (metHb), reticulocyte (ret) and Heinzbody (Hbd) on d0 before treatment and on d3, d5, d7, d10, d14 and d21 after treatment. The results showed that after drug administration the levels of metHb, ret and Hbd in PQ group increased on d3-d5, and reached their peak levels on d7-d10, and then declined gradually from d10-d14. The mean percentage concentration of metHb, mean count of ret and Hbd in PQ group on d7 after medication were 22.1 +/- 21.8%, 92.0 +/- 88.0/1,000 RBC and 203.8 +/- 126.7/1,000 RBC, which were significantly higher than those of the control (8.2 +/- 5.3%, 37.5 +/- 16.2/1,000 RBC and 57.4 +/- 45.1/1,000 RBC). In M8506 group, the mean Hbd count (196.3 +/- 123.1/1,000 RBC, on d7 after treatment was also higher than that of the controls, but its mean metHb percentage concentration (10.8 +/- 8.9%) and mean ret count (42.2 +/- 20.3/1,000 RBC) were similar to those of the controls (P > 0.05). The results suggested that the hemolytic toxicity induced by M8506 in rabbits might be similar to or even lower than that induced by PQ.
Shi
X
X
Institute of Parasitic Diseases, Chinese Academy of Preventive Medicine, Shanghai.
Zhan
C
C
Ha
S
S
Yiao
J
J
D000743:Anemia, Hemolytic / Q000139:chemically induced; D000818:Animals; D000962:Antimalarials / Q000633:toxicity*; D005260:Female; D006461:Hemolysis / Q000187:drug effects*; D008297:Male; D008708:Methemoglobinemia / Q000139:chemically induced; D011319:Primaquine / Q000031:analogs & derivatives* / Q000633:toxicity*; D011817:Rabbits
D000962:Antimalarials; C069677:M 8506; D011319:Primaquine