MODULATION OF CHLORAMPHENICOL(C) BIOAVAILABILITY(F) BY PANCREATIC ENZYME REPLACEMENT (PRE) IN CYSTIC FIBROSIS (CF)

Abstract

The effect of PER on the F of C was ascertained in 5 adolescent: patients with CF. Each patient was studied on 6 occasions separated by at least 24 hours. Exocrine pancreatic function was ascertained by the urinary excretion of PABA following ingestion of N-benzoyl-L-tyrosyl PABA. C was administered as C succinate(CS) intravenously, and C palmitate(CP) or C base (CB) orally at a dose of 20mg/kg with or without PER. Multiple timed blood samples were obtained over a 12 hour period following each dose and analyzed by HPLC. Model independent pharmacokinetic analysis of CS biodis-position revealed (x̄±SD) t½, 3.35±1.16hr; Vd_ss,1.39± 0.49 4kg; and Clp, 267.33±53.96ml/min/1.73m². These values were comparable to those obtained with CB and for CS in unaffected individuals. The absolute F of CB ranged from 71-154% without PER and increased by 8-17% after PER. For CP the absolute F ranged from 21-59% increasing by 2-200% following PER. In one patient CP absorption continued throughout the monitoring period after PER. The wide range of effect of PER on the F of the oral formulations of C appeared related to the level of intrinsic exocrine pancreatic function.The relative F, CP/CB, was directly related to urinary PABA excretion (r=0.9). These results suggest that PER may significantly enhance the F of CP through replacement of pancreatic lipase. Pancreatic enzymes may play a role in enhancing the F of CB as well.

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