ABSORPTION, EXCRETION AND TISSUE DISTRIBUTION OF SULFOCILLIN ADMINISTERED PARENTERALLY IN MICE, RATS, RABBITS AND DOGS

Abstract

The plasma level and tissue distribution of sulfocillin administered by intravenous, intraperitoneal, intramuscular or subcutaneous routes into mice, rats, rabbits and dogs, were compared with those of carbenicillin. The drug level was measured as active penicillin by a biological assay method using Bacillus subtilis PCI 219 as a test organism. The recovery rates of penicillins from the mixture with phosphate buffer homogenates of the tissues in vitro varied depending on the individual tissues and animal species, and in many cases the recovery rate of sulfocillin was higher than that of carbenicillin. A single dosage of sulfocillin or carbenicillin in all administration routes produced the highest plasma and tissue levels 5-15 minutes after injection in all animal species tested. Measurable concentrations of penicillin in plasma and tissues were detected up to 2 hours after administration in mice and rats, whereas they were detectable for 4-6 hours after intramuscular injection in rabbits and dogs. The levels of sulfocillin and carbenicillin in the liver and kidney were higher than in plasma in mice and rats, but not in rabbits. On the other hand, the levels of both penicillins in the lung and spleen were lower than in plasma and no measurable concentration of penicillin was detected in the brain. Urinary and biliary excretions of sulfocillin and carbenicillin were also studied. Amounts of both penicillins recovered from the 6-hour urine or bile sample in rabbits were similar. However, when sulfocillin and carbenicillin were given in dogs, the recovery rates in urine and bile were markedly different. When sulfocillin was administered, as much as 20% of the given dose was recovered in the 6-hour urine and about 50% of dose was recovered in the 6-hour bile. On the other hand, with carbenicillin, about 65% of the dose was recovered in the 6-hour urine and about 23% of the dose was recovered in the 6-hour bile.