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Surfactant protein A (SP-A), the major hydrophilic protein specifically associated with surfactant, has multiple metabolic and host defense functions as well as primary surfactant biophysical functions in association with the other surfactant proteins and lipids. To characterize its kinetics of secretion and clearance from the airspace, we measured specific activity-time curves for alveolar and lamellar body associated SP-A following the intravascular and/or intratracheal administration of the radiolabeled precursors Tran 35S-label containing primarily methionine and cysteine or [3H]methionine to newborn and adult rabbits. Alveolar SP-A specific activity peaked 30 min after precursor injection in both newborn and adult rabbits, and labeled SP-A was not detected in lamellar bodies until after 2 h. In newborns, a second peak of labeled SP-A appeared at 15 h. In both newborns and adult rabbits, lamellar body specific activity-time curves were most consistent with SP-A entering lamellar bodies via a recycling pathway from the airspaces. The airspace clearance of SP-A in adult rabbits had a biologic half-life of about 4.5 h. There was very little decrease in SP-A specific activity in the newborn rabbits, indicating minimal catabolism. These studies demonstrate secretion of endogenously synthesized SP-A by a pathway separate from lamellar bodies. The kinetics of secretion of SP-A and the surfactant phospholipid in newborn and adult rabbits indicate separate metabolic pathways.

Difficulties encountered in controlling theophylline blood concentrations in an asthmatic patient on hemodialysis prompted us to study the effect of hemodialysis on theophylline kinetics. Plasma theophylline extraction ratios, clearances, and half-lives were determined during dialysis for 11 adults given an intravenous infusion of 4 mg/kg aminophylline. For comparison, eight of these patients were evaluated for theophylline half-lives when not dialyzed. Extraction ratios of theophylline during dialysis ranged from 0.22 to 0.51 (0.35 +/- 0.08) for these patients, indicating that a mean of 36 per cent plasma theophylline was removed during each pass through the dialyzer. This compares with a mean extraction ratio of urea of 0.63 +/- 0.07. Plasma clearance of theophylline during dialysis ranged from 52 to 124 ml/min (83 +/ 20 ml/min). Plasma theophylline half-lives during dialysis ranged from 1.6 to 3.4 hours (2.3 +/- 0.5 hours). Theophylline half-lives when not on dialysis ranged from 3.5 to 8.2 hours (5.0 +/- 1.7). Theophylline clearance was significantly faster in every patient during dialysis. Asthmatics requiring hemodialysis should receive additional theophylline during dialysis if therapeutic blood levels are to be maintained. Routine hemodialysis will significantly increase clearance in a toxic patient in whom life-threatening toxicity is occurring and charcoal hemoperfusion is unavailable.

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