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Comparative pharmacokinetics of trypan blue in female Sprague-Dawley and Long-Evans rats
Administration of trypan blue to pregnant Sprague-Dawley or Long-Evans rats, during an identical stage of embryogenesis, has been associated with malformations in 97 and 17% of the offspring, respectively (Gunberg, Anat. Rec. 1958, 130, 310). In the present study the comparative pharmacokinetics of trypan blue in the two strains were investigated. Female Sprague-Dawley and Long-Evans rats were injected sc with 10 mg trypan blue/rat [0.5 ml 2% (w/v) trypan blue in distilled water]. Blood samples were collected from the post-orbital plexus at times ranging from 5 min to 480 hr after dosing. The peak serum concentration of trypan blue was greater in Sprague-Dawley rats. Pharmacokinetic analyses of concentrations of trypan blue in serum resulted in fitting a two-compartment open model, with first order absorption, for both strains. Elimination of trypan blue from the central compartment was faster in Sprague-Dawley rats. This phenomenon was associated with a net movement out of the central compartment, predicted by the ratio of intercompartment rate constants. It is possible that the reported differences between the two strains in the teratogenic effects of trypan blue could be attributable, in part, to these observed pharmacokinetic dissimilarities.
Administration of trypan blue to pregnant Sprague-Dawley or Long-Evans rats, during an identical stage of embryogenesis, has been associated with malformations in 97 and 17% of the offspring, respectively (Gunberg, Anat. Rec. 1958, 130, 310). In the present study the comparative pharmacokinetics of trypan blue in the two strains were investigated. Female Sprague-Dawley and Long-Evans rats were injected sc with 10 mg trypan blue/rat [0.5 ml 2% (w/v) trypan blue in distilled water]. Blood samples were collected from the post-orbital plexus at times ranging from 5 min to 480 hr after dosing. The peak serum concentration of trypan blue was greater in Sprague-Dawley rats. Pharmacokinetic analyses of concentrations of trypan blue in serum resulted in fitting a two-compartment open model, with first order absorption, for both strains. Elimination of trypan blue from the central compartment was faster in Sprague-Dawley rats. This phenomenon was associated with a net movement out of the central compartment, predicted by the ratio of intercompartment rate constants. It is possible that the reported differences between the two strains in the teratogenic effects of trypan blue could be attributable, in part, to these observed pharmacokinetic dissimilarities.