The nasal absorption of sodium cromoglycate in the albino rat

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Abstract
The intranasal absorption of sodium cromoglycate has been investigated in the adult male COBS/Wistar rat. Sodium cromoglycate (1 mg kg−1) was instilled into the nasal cavities and for comparison animals were also similarly dosed intravenously or sublingually. Serial samples of blood or bile were collected. After intravenous administration, the area under the plasma concentration curve (AUC0-∞) was 32 μg min ml−1 corresponding to a plasma clearance of 13 ml min−1 and an elimination rate constant of 0.049 min−1. Plasma concentrations of radioactivity after intranasal administration rose to a mean peak of 0.3 μg ml−1 approximately 20 min after dosing and fell to 0.03 μg ml−1 at 3 h. The AUC0-3 was 19 μg min ml−1 corresponding to an absorption of 60% over 3 h. The absorption rate constant (ka) was 0.059 min−1. The total amount of sodium cromoglycate excreted in bile after intravenous administration was 56%. The amount of compound excreted in the bile was 30% after intranasal administration corresponding to an absorption of 53%. Plasma and bile data therefore show good agreement. Total excretion in the bile over 3h after sub-lingual administration was 3%, demonstrating that this route made no significant contribution to the intranasal results. The absorption of sodium cromoglycate is independent of variations in the technique including changes in the orientation of the rat or blocking of the nasopalatine. The techniques used minimized other competing nasal clearance processes such as mucociliary clearance.