{'fraction_non_alphanumeric': 0.04456233421750663, 'fraction_numerical': 0.0259946949602122, 'mean_word_length': 5.245033112582782, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Role of serum protein binding and multiple antibiotic doses in the extravascular distribution of ceftizoxime and cefotaxime

The extravascular penetration of ceftizoxime and cefotaxime was studied in a rabbit subcutaneous Visking chamber model. Four rabbits, implanted with four chambers each, received each drug intramuscularly at a dose of 50 mg/kg every 3 hours for eight doses. Serum drug concentrations were measured after the eighth dose, and extravascular (chamber) concentrations were measured after the first and eighth doses. Cefotaxime (93% bound to rabbit serum proteins) demonstrated a much lower peak chamber-to-peak serum percent penetration after the first dose (20/163 = 13%) than did the less-bound (32%) ceftizoxime (21/52 = 40%, P less than 0.002). Similarly, the ratio of the chamber fluid area under the curve to the serum area under the curve was significantly lower for cefotaxime (15%) than for ceftizoxime (44%, P less than 0.002) after the first dose. Both agents approached equilibrium conditions between the intravascular and extravascular space by the eighth dose, and the ratios of chamber area under the curve to serum area under the curve of cefotaxime (76%) and ceftizoxime (79%) were similar. The peak-to-peak percent penetration of ceftizoxime (54%) was still significantly higher than that of cefotaxime (41%, P less than 0.01), although the chamber concentration of cefotaxime (66.2 micrograms/ml) was considerably higher than that of ceftizoxime (28.2 micrograms/ml). This study illustrates (i) dampened peak-to-trough antibiotic level fluctuation seen at extravascular sites as compared with measured serum concentrations, (ii) the large differences in extravascular penetration between single- and multiple-dose studies, and (iii) the importance of serum protein binding in the delay, but not the prevention, of extravascular drug distribution.