Age related changes in the clearance and oral absorption of sodium cromoglycate in the developing albino rat

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Abstract
A dual radioisotope method was used to investigate the clearance and oral abso***rption of sodium cromoglycate. Radiolabelled sodium cromoglycate was administered orally at a dose of 100 mg kg 1 (14 C-labelled) and simultaneously subcutaneously at a dose of 2 mg kg−1 (3 H-labelled) to rat pups 5, 9, 14, 20, 29 and 75 days old. Blood concentrations of 14 C and 3 H were measured at intervals for 24 h after dosing. Since the compound is not metabolized the blood concentrations of 14 C were taken as a measure of the sodium cromoglycate absorbed orally and the blood concentrations of 3 H as a measure of the subcutaneously administered material. Using the area under the oral 14 C blood curve (AUC) as an index of bioavailability, the calculated bioavailability of sodium cromoglycate (692·9−945·9 min μg ml−1) in 5, 9 and 14 day old pups was 4–8 times greater than that observed (61·0-118·8 min μg ml−1) in 20, 29 and 75 day old pups. The blood clearance of sodium cromoglycate was increased four-fold in 75 day old animals (43·9 ml min−1 kg−1) and three-fold in 20 and 29 day old pups when compared to the clearance in 5, 9 and 14 day old pups. The clearance in 5, 9 and 14 day old pups was relatively constant (10·8 − 9·9 ml min−1 kg−1). In rats less than 14 days old the systemic absorption of sodium cromoglycate after oral administration was 2–3 times greater (6·8-9·2%) than in rats aged 20, 29 or 75 days old (2·7-3·3%). The reduction in oral bioavailability of sodium cromoglycate as the pups grew older was, therefore, due to both an increased blood clearance and a decreased absorption of the compound.