Individuals with cystic fibrosis (CF) have altered kinetics for a number of drugs, most often an increased volume of distribution ( Vd) per body weight and increased clearance per body weight. To further evaluate those differences, we studied bromide kinetics (Vd, elimination rate constant, and clearance) and body mass index in eight adults with mild-to-moderate forms of CF, 21 obligate carriers of the CF gene, and 21 healthy controls. Bromide distribution approximates the extracellular fluid volume and bromide is excreted unchanged by the kidney.
Individuals were given a single oral dose of bromide (50 mg/kg), and serum bromide concentrations were measured over 4 weeks. Bromide pharmacokinetics (Vd, elimination rate constant, and clearance) were determined using a one-compartment model with first-order kinetics. Body mass index was determined for each individual.
Individuals with CF had a significantly greater lean body mass per kilogram as estimated by body mass index compared with individuals in the obligate carrier and control groups. The mean (±SD) Vd per kilogram for the CF group (311 ±29 mL/kg) was significantly greater than that of the obligate carrier group (261±26 mL/kg) and the control group (274±30 mL/kg). However, the mean (±SD) Vd per square meter for the three groups was similar. The mean elimination rate constant for the CF group (3.55±0.98×10−3/h) was significantly greater compared with the mean elimination rate constant for the obligate carrier group (2.55±0.36×10−3/h) and the control group (2.58±0.49×10−3/h). The mean (±SD) clearance per kilogram was also significantly greater for the CF group (1095 ±283 μL/kg per hour) compared with the obligate carrier group (664±100 μL/kg per hour) and the control group (700±115 μL/kg per hour).
These findings indicate that individuals with CF have a greater Vd per kilogram for bromide and drugs that distribute in the extracellular fluid volume because of their greater lean body mass per kilogram. The findings also suggest that individuals with CF have a greater renal clearance of bromide and presumably of other anionic drugs excreted by the kidney. The results emphasize the importance of body composition in drug disposition.(Arch Pediatr Adolesc Med. 1994;148:266-271)