Interindividual differences in o,p'-DDD enantiomer kinetics examined in Göttingen minipigs.
Five minipigs were given a single oral dose of a racemic mixture of o,p'-DDD (30 mg kg(-1)b.w., EF=0.49). Blood plasma and subcutaneous adipose tissue were collected for analysis, at different time-points over 180 d. At the end of the experiment also liver, kidney and brain tissue were collected. Low concentrations of o,p'-DDD still remained after 180 d in plasma (mean 0.5+/-0.3 ng g(-1)f.w.) and in adipose tissue (mean 40+/-40 ng g(-1)f.w.). The mean concentrations in liver and kidney were 500+/-300 pg g(-1)f.w. and 90+/-50 pg g(-1)f.w., respectively. The enantiomers of o,p'-DDD were isolated by HPLC and the absolute configuration of the enantiomers were determined by X-ray crystallography and polarimetry as R-(+)-o,p'-DDD and S-(-)-o,p'-DDD. The enantiomer fractions (EFs) of o,p'-DDD were determined in plasma, adipose tissue and kidney using GC/ECD equipped with a chiral column. The EFs of o,p'-DDD in the individual minipigs showed large variability, ranging from 0.2 to 0.6 after 24h in plasma and from 0.2 to 0.7 after 90 d in adipose tissue. Hence in two of the minipigs, the S-(-)-o,p'-DDD enantiomer was dominating while the other enantiomer, R-(+)-o,p'-DDD was dominating in three minipigs. We propose that a yet not identified factor related to polymorphism, regulating the metabolism and/or elimination of the enantiomeric o,p'-DDD, is responsible for the differences in enantiomeric retention of the compound in the minipigs.
Cantillana
T
T
Department of Environmental Chemistry, Stockholm University, SE-106 91 Stockholm, Sweden. tatiana@mk.su.se
Lindström
V
V
Eriksson
L
L
Brandt
I
I
Bergman
A
A
D000284:Administration, Oral; D000818:Animals; D002849:Chromatography, Gas; D018360:Crystallography, X-Ray; D007700:Kinetics; D008939:Mitotane / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics*; D013237:Stereoisomerism; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D014018:Tissue Distribution
D008939:Mitotane