The fate of infused spermidine in the plasma of rats.

An elevation of the plasma spermidine concentration might indicate whether administration of a cytostatic drug harms tumour cells. Such elevations, however, are only small. By infusing various amounts of spermidine into the circulation of rats, spermidine plasma elevations were evoked artificially. During 2.5 h infusion and 1.5 h after infusion spermidine plasma concentrations were measured. It appeared that total amounts of 0.031 and 0.4 mg did not give an appreciable elevation of plasma spermidine concentrations above basic levels. Infusion of 1.0 mg gave rise to an elevation but already showed a trend towards normal levels during the infusion. There is evidence for a first-pass lung effect for spermidine. Blocking of monoamine and diamine oxidase enzymes resulted in a further elevation of spermidine concentrations above basic levels. Which of the two enzymes is the more important for spermidine catabolism could not be determined.

Influence of Intralipid infusion on the elimination of phenytoin.

On the ground of clinical observations the hypothesis was tested that a changed disposition of phenytoin could bring about a shortened half-life. In vitro it appeared that the amount of phenytoin bound to the Intralipid fraction was more than twice the amount present in the plasma fraction. In an in vivo rat model it was shown that the half-life of phenytoin was indeed influenced by Intralipid administration, but contrary to clinical observations phenytoin half-life was prolonged. Some possible explanations for this discrepancy are discussed.

Folic acid and the protective action of diphenylhydantoin against maximal electroshock in rats after single doses.

Conflicting evidence regarding the antagonistic action of folic acid (FA) on the efficiency of the antiepileptic drug diphenylhydantoin (DPH) led us to study this problem in rats. From the results it is concluded that the enteral absorption of particularly higher doses of DPH is slightly hampered by FA. When the dose of DPH is high enough, this diminished absorption will not manifest itself in impaired protection. On the basis of DPH levels in brain tissue it is concluded that also on brain level there is some antagonistic action of FA on DPH protection. Here too, a sufficiently high level of DPH prevents this antagonistic action from becoming evident. We suggest that only in patients in whom the DPH treatment is marginal, FA treatment may hamper the therapeutic antiepileptic effect.

Suction blister fluid as a model for interstitial fluid in rats.

1. Suction blisters on the skin of rats, obtained with a negative pressure of 150 mm Hg, show a close similarity to human suction blisters, based on histological, electrolyte and protein findings. 2. Pharmacokinetic experiments with inulin and antipyrine have proved that the movement of these low protein binding drugs between blister fluid and serum follows the laws of diffusion. 3. The investigations suggest that blister fluid resembles interstitial fluid and can therefore serve as a model for the estimation of drug concentrations in interstitial fluid.