bulaquine and Methemoglobinemia

Methemoglobin, a toxic ferric form of hemoglobin, is continuously formed in normal erythrocytes, but during abnormal situations in situ, the level is enhanced. 8-Amino-quinolines and related compounds are causative agents for methemoglobin formation. Employing oxyhemoglobin, methemoglobin toxicity was about six times higher with primaquine compared to CDRI Compound 80/53 at 10(-9) M concentration. Methemoglobin reductase activity was also completely inhibited by primaquine, whereas 24% inhibition was noted in the case of 80/53 at the same concentrations. Mastomys, a rodent animal model, was found to be equally good for comparative evaluation of methemoglobin toxicity. Further, with the use of primaquine transdermal tape on the Mastomys model, a rise in methemoglobin occurred with increase in time. In conclusion, the study presents simple, economical, less time-consuming methods for the evaluation of methemoglobin toxicity, in vitro and in vivo, without employing the conventional Beagle dog model.

Topics: Administration, Cutaneous; Administration, Oral; Aminoquinolines; Animals; Antimalarials; Artemisinins; Cell-Free System; Chloroquine; Cytochrome-B(5) Reductase; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Erythrocytes; Macaca mulatta; Methemoglobin; Methemoglobinemia; Muridae; Oxyhemoglobins; Primaquine; Rats; Sesquiterpenes

Methemoglobin toxicities of primaquine and compound N1-(3-acetyl-4-5-dihydro-2-furanyl)-N4-(6-methoxy-8-quinolinyl) 1,4-pentanediamine, CDRI Code 80/53, have been compared in beagles. Primaquine administration at 3 mg/kg for 7 days produced significantly high (P less than 0.001) methemoglobinemia and the levels increased 10.55-fold. Compound 80/53 at 3.75 mg/kg x 7 days produced a marginal increase in methemoglobinemia (3.24-fold; P less than 0.02). The methemoglobin formed by primaquine administration was 3.65-fold (P less than 0.001) higher than that formed after administration of compound 80/53. There was no significant change in other hematological parameters and liver function tests.

Topics: Aminoquinolines; Animals; Antimalarials; Appetite; Body Weight; Dogs; Female; Male; Methemoglobinemia; Primaquine