Influence of gestation on the pharmacokinetics of four sulphonamides in goats.
The influence of gestation on the pharmacokinetics of four sulphonamides was studied in goats before, during and after pregnancy. Similar doses were given as intravenous boluses of 50 mg kg-1 each. Results were compared with those of non-pregnant goats to eliminate seasonal effects. With sulphadimidine elimination was mainly apparently first-order. In gestating goats the mean residence times decreased and mean plasma clearance rates increased with sulphadimidine during pregnancy, but this effect was continued after kidding at least until the end of May. The same happened with sulphadimethoxine, but sulphisomidine was not affected. In contrast to the other sulphonamides the mean residence time of sulphadoxine showed a maximum in February in gestating goats, while mean plasma clearance remained constant during and after pregnancy, at a lower level than in September. The mean plasma clearance of sulphadoxine decreased significantly from September to February in the non-pregnant control goats. In May five of six control goats and two of six goats which had kidded showed capacity-limited elimination against only two control goats in the foregoing experiments. With sulphadoxine one animal in the gestation group, but not the same one in each experiment, showed capacity-limited elimination against one, four and three in the control group in December, February and May, respectively. Distribution volumes increased significantly during and after pregnancy with sulphisomidine and sulphadimethoxine. A decrease in distribution volumes was seen in control goats with sulphadimidine, sulphisomidine and sulphadoxine, but was only significant for sulphadoxine. The pregnant uterus could not be recognised as an extra compartment, either in distribution volume nor in the pharmacokinetic model.(ABSTRACT TRUNCATED AT 250 WORDS)
Van Gogh
H
H
Department of Veterinary Pharmacology, Pharmacy and Toxicology, State University of Utrecht, The Netherlands.
Van Deurzen
J M
JM
Van Duin
C T
CT
Van Miert
A S
AS
D000818:Animals; D005260:Female; D006041:Goats / Q000378:metabolism*; D049590:Postpartum Period / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D012621:Seasons; D013412:Sulfadimethoxine / Q000493:pharmacokinetics; D013413:Sulfadoxine / Q000493:pharmacokinetics; D013418:Sulfamethazine / Q000493:pharmacokinetics; D013443:Sulfisomidine / Q000493:pharmacokinetics; D013449:Sulfonamides / Q000493:pharmacokinetics*
D013449:Sulfonamides; D013412:Sulfadimethoxine; D013418:Sulfamethazine; D013413:Sulfadoxine; D013443:Sulfisomidine