PERMEABILITY OF THE RESPIRATORY-TRACT TO DIFFERENT-SIZED MACROMOLECULES AFTER INTRATRACHEAL INSTILLATION IN YOUNG AND ADULT-RATS

The markers, bovine IgG (BIgG, mol. wt = 150 000 Da) and bovine serum albumin (BSA, mol. wt = 67 000 Da) together with I-deamino-cysteine-8-D-arginine vasopressin (dDAVP, mol. wt = 1067 Da), were intratracheally instilled into young and adult rats and their passages via the respiratory tract were assessed as immunoreactive marker levels in blood serum. In the adult rats (100-200 days old) the BSA serum levels peaked 16-24 h after instillation and with a calculated transferred amount (bioavailability) of 4.3 ± 1.7 to 5.6 ± 1.4% of the dose given (five resp. 50 mg kg-1 body wt). BIgG passed via the respiratory tract with a maximum at 16 h, and with a transferred amount of 1.5 ± 0.3%, while dDAVP serum levels peaked at 1 h and with a transferred amount of 20 ± 4%. For the 30-day-old rats, similar passage time curves were obtained as for the adult, but the transferred amount was lower for BIgG (0.7 ± 0.3%), similar for BSA (4.1 ± 1.1%) and higher for dDAVP (45 ± 16%). The serum levels of BSA increased linearly with increasing dose instilled (2.5-200 mg kg-1 body wt), indicating a passive transepithelial transport route. The results show that macromolecules pass via the respiratory tract into the circulation of the rat in mainly intact forms and in high amounts, compared with passage via the GI tract. There appears to exist an inverse relationship between the molecular weights of instilled molecules and the transferred amount, a relationship affected by the development of the lung.