Interrelationship between the pharmacokinetics and pharmacodynamics of cefaclor advanced formulation in patients with acute exacerbations of chronic bronchitis

Cefaclor advanced formulation (cefaclor AF) is an extended-release form of the oral cephalosporin cefaclor, When cefaclor AF 750 mg twice-daily and cefaclor immediate release 500 mg three-times-a-day are compared there is a skew to the right of the pharmacokinetic profile and higher levels are achieved, Based on this pharmacokinetic finding, we examined the relationship between the bacterial susceptibility to cefaclor (MIC), the achieved cefaclor AF serum and sputum concentrations, and in vivo eradication of the bacteria in 36 patients with acute exacerbations of chronic bronchitis. The mean peak concentrations in serum and sputum 5 h after administration were 8.6 mu g/ml (95% CI: 8.1 mu g/ml - 9.1 mu g/ml) and 1.5 mu g/ml (95% CI: 1.4 mu g/ml - 1.7 mu g/ml), respectively. Cefaclor was always detectable 8 h after administration. At post therapy, treatment was successful in 31 (86.1%) patients. Cefaclor concentrations in serum persisted above the MIC for more than 40% of dosing interval in 31 subjects, and those in sputum in 24 patients. Treatment was successful in all subjects with percent of time above the MIC in serum of >40%, whereas the time that levels in sputum stayed above the MIC was not the pharmacodynamic parameter that correlated best with therapeutic efficacy for cefaclor, Our data demonstrate that when cefaclor AF is dosed twice-daily, the in vivo pharmacodynamic susceptibility breakpoint is 8 mu g/ml. The good activity and pharmacokinetics of cefaclor AF provide serum concentrations higher than the MIC of Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis for more than 40% of the Validated dosing interval. Therefore, it might be considered for first choice treatment of acute exacerbations of chronic bronchitis.