EFFECT OF PLASMA-BINDING OF ORTHO-BENZOATES AND PARA-I-BENZOATES ON THEIR DISTRIBUTION IN BLOOD AND INTO LYMPH, BIOTRANSFORMATION AND EXCRETION IN RAT URINE

Two positional iodine derivatives of benzoic acid i.e. ortho- (OIB) an d 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 biotransformat ion 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 S A of the free faction of drug in lymph was shown only with PIB. Kineti c parameters of benzoates are influenced by plasma binding; significan t differences were found mainly in total clearance and areas under con centration curves. Lymphatic bioavailability (F-L) differs only slight ly with different plasma binding; a significant change in F-L was, how ever, found in PIB after SA premedication. Significantly higher urinar y 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 metabo lites of benzoates in urine.