Pharmacokinetics of three sulphonamides in ruminant and preruminant kids.
The pharmacokinetic properties of three sulphonamides were determined in ruminant and preruminant kids after oral and intravenous administration. First, sulphisomidine (SIM, 50 mg kg-1) and sulphadoxine (SDX, 30 mg kg-1) were given to seven kids, 10 to 12 weeks old, while on a milk replacer diet and again at 15 to 18 weeks when fed roughage. Secondly, SIM (100 mg kg-1) and sulphadimidine (SDD, 100 mg kg-1) were given at six to nine, 12 to 15 and 18 to 21 weeks old to eight kids, of which four were fed milk replacer and four were with their mothers (with access to roughage) until 15 weeks, after which all were fed roughage only. SDX and SDD exhibited non-linear (or capacity limited) absorption after oral dosage, suggesting possible active absorption mechanisms, and both drugs also showed non-linear elimination. Intravenous curves for SDD and SIM indicated that recycling occurred. With SDX, ruminant kids showed poorer systemic availability after oral dosage, shorter t1/2(el) and higher B than did preruminants. For SDD, ruminant kids had lower Vd and higher B than preruminants. SIM's t1/2(el) tended to shorten and beta to increase in both groups throughout the experiment. Not all differences between ruminants and preruminants in sulphonamide pharmacokinetics could be explained by the accumulation of acidic forestomach contents and the change of urine pH from acid to alkaline in the maturing ruminant. Other potential contributing factors require investigation, including possible alterations in hepatic drug metabolism. Of the three drugs tested, SDX might be the most satisfactory for therapeutic use in preruminant animals, because it has good bioavailability after oral administration and long t1/2(el).
Concentrations of sulfadoxine and trimethoprim in plasma, lymph fluids and some tissues 24 h after intramuscular administration to Angora goats.
This study was carried out to determine the concentrations of sulfadoxine and trimethoprim in plasma, lymph, and some tissues in goats after administration of a single recommended therapeutic dose. Five healthy, adult Angora goats were used. The drug combination, containing 200 mg sulfadoxine and 40 mg trimethoprim per millilitre, was given as a single IM injection at the recommended dose level, 15 mg/kg body weight for sulfadoxine and 3 mg/kg body weight for trimethoprim. The goats were slaughtered 24 hours after drug administration and samples were taken from liver, bone marrow, pelvic limb muscles, hepatic, thoracic duct, and the pelvic limb lymph fluids for analysis of drug concentrations by HPLC. The concentrations of trimethoprim in bone marrow, liver, pelvic limb muscles, hepatic lymph, the pelvic limb lymph, and thoracic duct lymph were found to be 6, 5, 4, 2, 5 and 15 times higher than those of plasma, respectively. Although the sulfadoxine concentrations in bone marrow, pelvic limb muscles, and liver were 2, 3 and 2 times higher than the plasma concentrations, respectively, the sulfadoxine concentrations in hepatic lymph, the pelvic limb lymph, and thoracic duct lymph were lower than those of plasma. The results show that the trimethoprim concentrations in lymph fluids were quite similar to those in tissues. However, the sulfadoxine concentrations in lymph fluids were different in each tissue.
Effeets of etiocholanolone‐indueed fever on plasma antipyrine half‐lives and metabolie elearanee
The plasma half‐life and metabolie clearanee rate of antipyrine, a drug metabolized by hepatie microsomal enzymes, were determined in 33 normal volunteers du ring a basal state and during fever indueed with a single intramuseular injeetion of etioeholanolone. Of the 14 normal volunteers who aehieved signifieant fever (fever index> 50), in 11 plasma antipyrine half‐life was prolonged after a single oral dose of 10 mg/kg and antipyrine metabolie clearanee rate was deereased. There was no signifieant ehange of these mean values in 19 normal volunteers who failed to develop signifieant fever (fever index <50). Therefore, under the eonditions of this study plasma antipyrine half‐life was prolonged, probably due to impaired hepatie metabolism, during etiocholanolone‐indueed fever, although no eorrelation was observed between the magnitude of fever and the extent to whieh plasma antipyrine half‐life was prolonged. Failure to obtain sueh a eorrelation may be attributable to the very small range of temperature elevation, extending from 37.9° C to 39.2° C, in the group of 14 subjeets achieving signifieant etioeholanolone‐indueed fever (fever index > 50). A higher dose of antipyrine (18 mg/kg) suppressed induetion of fever by etiocholanolone; antipyrine is the only orally administered drug thus far shown to be effeetive in repressing etiocholanolone‐indueed fever.