Aarons L, Rowland M, Khan A, Taborelli G, Ferrea G, Tarantino V, Fioredda F, Rosina-Parenti R, Cavenaghi L, Borgonovi M
School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester M13 9PL, UK.
Eur J Pharm Sci. 1998 Oct;6(4):265-70. doi: 10.1016/s0928-0987(97)10015-x.
The population pharmacokinetics of teicoplanin in plasma and tonsillar tissue in children was determined following intramuscular administration. Thirty seven patients in all received either a single 5 mg/kg dose; 2 doses of 5 mg/kg, 12 h apart; 3 doses of 5 mg/kg, 12 h apart; or, a single 10 mg/kg dose. Limited data, comprising a maximum of 2 blood samples and 1 tonsillar sample were taken from each patient, with the maximum time being 48 h after the first dose of teicoplanin (in the 3 x 5 mg/kg dosing schedule). All plasma data were analyzed simultaneously by a maximum likelihood method employing a modified EM algorithm. A first-order absorption, one-compartment disposition model was fitted to the data. Mean parameter values (with lower and upper 95% confidence intervals) were: clearance/bioavailability, 0.024 L h(-1) kg(-1) (0.020-0.027); volume of distribution/bioavailability, 0.61 L kg(-1) (0.54-0.70); absorption rate constant, 0.43 h(-1) (0.31-0.61). A first-order transfer model for distribution of teicoplanin between plasma and tonsillar tissue was fitted to the tonsil data. The mean parameter values (95% confidence intervals) were: transfer rate constant between plasma and tonsils 0.49 h(-1) (0.35-0.67); transfer rate constant between tonsils and plasma 0.73 h(-1) (0.52-1.03). These rate constants correspond to a distribution half-life of 0.95 h and an equilibrium distribution concentration ratio between tonsillar tissue and plasma of 0.67. After normalising clearance and volume of distribution for body weight, there was no further influence of body weight on the pharmacokinetic parameters. Also, there was no effect of dose, and as two formulations were used, one for the 5 mg/kg dose and the other for the 10 mg/kg dose, no effect of formulation on the pharmacokinetics of teicoplanin after im (intramuscular) administration was found.
在儿童中，肌内注射替考拉宁后测定了其在血浆和扁桃体组织中的群体药代动力学。共有37名患者接受了以下治疗：单次5mg/kg剂量；2次5mg/kg剂量，间隔12小时；3次5mg/kg剂量，间隔12小时；或单次10mg/kg剂量。从每位患者身上采集的数据有限，最多包括2份血样和1份扁桃体样本，最长时间为首次注射替考拉宁后48小时（在3×5mg/kg给药方案中）。所有血浆数据均采用改进的期望最大化（EM）算法通过最大似然法进行同时分析。对数据拟合了一级吸收、单室处置模型。平均参数值（及95%置信区间下限和上限）为：清除率/生物利用度，0.024L·h⁻¹·kg⁻¹（0.020 - 0.027）；分布容积/生物利用度，0.61L·kg⁻¹（0.54 - 0.70）；吸收速率常数，0.43h⁻¹（0.31 - 0.61）。对扁桃体数据拟合了替考拉宁在血浆和扁桃体组织之间分布的一级转运模型。平均参数值（95%置信区间）为：血浆与扁桃体之间的转运速率常数0.49h⁻¹（0.35 - 0.67）；扁桃体与血浆之间的转运速率常数0.73h⁻¹（0.52 - 1.03）。这些速率常数对应的分布半衰期为0.95小时，扁桃体组织与血浆之间的平衡分布浓度比为0.67。将清除率和分布容积按体重进行标准化后，体重对药代动力学参数不再有进一步影响。此外，剂量没有影响，并且由于使用了两种制剂，一种用于5mg/kg剂量，另一种用于10mg/kg剂量，未发现制剂对肌内注射替考拉宁后的药代动力学有影响。
