Effect of plasma binding of ortho- and para-I-benzoates on their distribution in blood and into lymph, biotransformation and excretion in rat urine

Summary

Two positional iodine derivatives of benzoic acid, i.e. ortho- (OIB) and para- (PIB), were used alone and in combination with salicylic acid (SA) to study the effects of plasma binding on their pharmacokinetics. Their lymphatic bioavailability (central lymph), their biotransformation and urinary excretion in rats were also studied.

Plasma binding of the two benzoates is different, about 95% of PIB and approximately 50% of OIB are bound. The competitive inhibition effect of SA was shown by an increase in the amount of free drug in plasma in both benzoates. Lymphatic binding is lower compared to plasma binding, an effect of SA of the free faction of drug in lymph was shown only with PIB. Kinetic parameters of benzoates are influenced by plasma binding; significant differences were found mainly in total clearance and areas under concentration curves. Lymphatic bioavailability (F_L) differs only slightly with different plasma binding; a significant change in F_L was, however, found in PIB after SA premedication.

Significantly higher urinary excretion of OIB as compared with PIB corresponds to plasma binding of drugs, SA premedication decreases total excretion of both benzoates. SA also changes the proportion of the individual fractions of metabolites of benzoates in urine.