Pharmacokinetics of individual components of teicoplanin in man

Teicoplanin is a new antibiotic consisting of closely related glycopeptides. Following an iv bolus of 400 mg teicoplanin, the pharmacokinetics of the individual components A3-1, A2-1, A2-2, A2-3, A2-4, and A2-5 was studied in five healthy volunteers by HPLC. For each subject, plasma and urine data of the individual components were simultaneously fitted by a triexponential disposition model. No significant differences were observed between the components of the A2 group in the initial volume of distribution, 0.05-0.06 L/kg, and the half-life of the second disposition phase, 2.5-3.0 hr. Significant differences were found in the volume of distribution at steady state (Vss 0.42-0.92 L/kg), the half-lives of the first (0.18-0.26 hr) and the third (48.1-66.8 hr) disposition phases, the total clearance (CL 5.4-19.3 ml/hr per kg), the renal clearance (CLR 2.8-16.1 ml/hr per kg), and the percentage of the administered dose excreted in urine (Ae 53-85%). A highly significant correlation was found between the lipophilicity of the individual components increasing from A2-1 to A2-5, and the values of the kinetic parameters. As the lipophilicity increases the fraction unbound in plasma, Vss, CL, CLR, and Ae decrease, whereas the unbound steady state volume of distribution and the unbound nonrenal clearance increase. A modest degree of accumulation of each teicoplanin component in plasma is predicted to occur at steady state following repeated administration of teicoplanin given daily, with accumulation slightly higher for the more lipophilic components A2-4 and A2-5.