The nasal absorption of a range of water-soluble compounds with different molecular weights, 4-oxo-4H-1-benzopyran-2-carboxylic acid (mol. wt 190), p-aminohippuric acid (mol. wt 194), inulin (mol. wt 5200) and dextran (mol. wt 70,000), has been investigated in the male Wistar rat. Compounds were instilled into the nasal cavities of anaesthetized animals, and for comparison, similar doses were administered intravenously. Serial samples of bile and urine were collected for up to 6 h. Nasal absorption, estimated by comparison of the extent of excretion in bile and urine following intranasal and intravenous administration, was 100% for 4-oxo-4H-1-benzopyran-2-carboxylic acid (1 mg kg-1), 75% for p-aminohippuric acid (1 mg kg-1), 15% for inulin (0.1 mg kg-1) and 2.8% for dextran (0.25 mg kg-1). The log molecular weight gave a good linear correlation with the log per cent intranasally absorbed (correlation coefficient of -0.996). From the molecular weight relationship, these data infer aqueous channel mechanisms for the nasal absorption of water-soluble compounds.

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The relationship between the whole blood concentration of carbonic anhydrase and the biological half life of chlorthalidone has been investigated in six volunteers. A linear relationship was observed and on the basis of this, a pharmacokinetic model to explain the long and variable biological half life of chlorthalidone is proposed and discussed.

A gas chromatographic method has been used to determine chlorthalidone in amniotic fluid, maternal and foetal blood at delivery, and in maternal milk and blood three days after delivery, following the administration of chlorthalidone to nine pregnant women suffering from toxaemia of pregnancy. Placental transfer of chlorthalidone and elimination in maternal milk have been shown and the implications of these factors are discussed. An explanation has been proposed for our observations that foetal blood levels of the drug are about 15% of those in maternal blood.