hr-810 and Hemolysis

As a series of safety studies of cefpirome sulfate (CPR), its local irritancy was examined in rabbits after the following treatments: intracutaneous injection (single), application into the conjunctival sac of the eye (single), intramuscular injection (single, 7-day repeated), and intravenous injection (8-day repeated). In addition, the hemolysis test was carried out with human blood. When CPR was injected intracutaneously at a high concentration of 20%, its irritating effects were only equal to or slightly stronger than those of distilled water for injection and Na2SO4 solution. The same concentration of the compound applied into the conjunctival sac had little irritancy to the eye. In the single intramuscular administration experiment, muscular changes caused by 10% CPR were comparable to those by 0.75% acetic acid, slightly severer than those by physiological saline, and slighter than those by 6% acetic acid at 2 days after administration, but at 7 days, the changes were apparently slighter than those by 0.75% acetic acid. CPR is classified under Grade 3 according to the draft guidelines for local tolerability studies issued by the Ministry of Health and Welfare of Japan. The repeated intramuscular administration experiment showed the following results. Muscular changes caused by 10% CPR were comparable to those by physiological saline and slighter than those by 0.75% acetic acid, 5% cefotetan (CTT) and 20% cephalothin sodium (CET) at 2 days after the last administration. At 7 days, the changes were slightly severer than those by physiological saline, but slighter than those by the other control solutions. Microscopically, a tendency toward recovery was marked. In the vascular irritancy experiment, the 10% CPR group showed thrombus macroscopically on and after day 5 of dosing. Microscopy at the end of the 8-day administration period revealed thrombus and organized thrombus. In the 20% CET group, thrombogenesis was slighter than that in the 10% CPR group, while perivascular changes were severer. The changes caused by 5% CTT (thrombogenesis, perivascular changes) were somewhat severer than those by 10% CPR. In the hemolysis test, 10% CPR solution applied to fresh blood from adult men caused to hemolysis when determined by the macroscopic or spectrophotometric method.

Topics: Animals; Cefpirome; Cephalosporins; Eye; Hemolysis; Irritants; Male; Muscles; Rabbits; Skin; Thrombosis