Induction of acetylating capacity with complete Freund's adjuvant and hydrocortisone in the rabbit

This study was undertaken to investigate whether modifications in the reticuloendothelial system (RES) activity induce changes in the extent of sulfamethazine (SMZ) acetylation. Five days prior to any RES stimulation or inhibition, pharmacokinetic parameters of SMZ and N-acetyl-SMZ were determined in albino rabbits following a SMZ dose of 20 mg/kg iv. Blood and urine samples were collected and analyzed spectrophotometrically. During the actual test period, one group of rabbits served as control, receiving 0.75 ml of a 0.9% NaCl solution per kg ip on day 0 and then one to seven doses of SMZ over the next 43 days. The effect of RES stimulation was assessed in a second group of rabbits receiving 0.75 ml of complete Freund's adjuvant (CFA) per kg on day 0 followed by seven iv injections of 20 mg of SMZ per kg over the next 43 days. Three groups of rabbits received known RES depressants: colloidal carbon (CC), 32 mg/kg iv; hydrocortisone (HC), 150 mg/kg iv for 10 days; cyclophosphamide (CTX), 15-75 mg/kg iv for 12 days. The administration of each of these compounds was accompanied or followed by one to seven in injections of 20 mg of SMZ per kg. The SMZ metabolic rate constant (km) was not affected in the control, CC, or CTX groups. CFA increased the SMZ km by 60 and 135% in fast and slow acetylators, respectively (p less than 0.05), and HC increased SMZ km by 39% (p less than 0.05). It is concluded that the acetylating capacity of rabbits may be induced by CFA and high doses of HC. Consequently, drug acetylation and RES activity appear to be independent.