Abstract
Objectives: The pharmacokinetics (PK) of teicoplanin differs in children compared with adults. Our aim was to determine the PK of teicoplanin in an Asian pediatric population and to optimize dosage regimens. Methods: This was a retrospective PK study and all the data were collected from hospitalized children. We developed a population PK model using sparse data, and Monte Carlo simulation was used to assess the ability of standard teicoplanin regimen and other different dosage regimens. The optimal dosing regimens were defined as achieving the target trough concentration (C min) of 10 mg/L and pharmacokinetic/pharmacodynamic (PK/PD, [AUC24/MIC]) of 125 for moderate infection. For severe infection, the optimal dosing regimens were defined as achieving the target 15 mg/L and AUC24/MIC of 345. Results: 159 children were included and 1.5 samples/children on average were provided. Estimated clearance of teicoplanin was 0.694 L/h (0.784/L/h/70 kg) and volume of distribution was 1.39 L. Teicoplanin standard loading dose was adequate for moderate infection, while 13 mg/kg was needed for severer infection. With standard maintenance doses, both patients with moderate and severe infection failed to achieve the target C min. 12 and 16 mg/kg/day were required to achieve a C min ≥ 10 and 15 mg/L, respectively. However, standard maintenance dose was adequate to achieve AUC24/MIC ≥ 125 for moderate infection, and 12 mg/kg/day was needed to achieve AUC24/MIC ≥ 345 for severe infection. Lower weight and serum creatinine were associated with higher dose. Conclusion: Optimal doses based on the target C min were higher than that based on the PK/PD target. To achieve the C min and PK/PD targets simultaneously, a standard loading dose was adequate for moderate infection based on simulation, while dosing higher than standard doses were required in other situation. Further clinical studies with rich sampling from children is required to confirm our findings.
Highlights
Teicoplanin is a glycopeptide antibiotic with activity against methicillin-resistant Staphylococcus aureus (MRSA) (Traina and Bonati, 1984)
If serum creatinine (SCr) readings were unavailable around the teicoplanin dosing (±48 h), the closest available SCr reading would be imputed
Data are expressed as n (%) or mean ± standard deviation unless specified otherwise. aCreatinine clearance was calculated by the Cockcroft formula. bThe number of patients co-medicated with at least one other anti-bacterial drug were summarized. cAdministered for three doses at the start of teicoplanin therapy
Summary
Teicoplanin is a glycopeptide antibiotic with activity against methicillin-resistant Staphylococcus aureus (MRSA) (Traina and Bonati, 1984). Teicoplanin trough concentration (Cmin) is closely associated with clinical efficacy. The proportion of children failing to achieve the target Cmin were 48–89% (Sanchez et al, 1999; Strenger et al, 2013; Zhao et al, 2015). The mean Cmin of teicoplanin were 4.8/5.7/ 5.9 mg/L at 24/72/168 h, respectively, after the first dose (Sanchez et al, 1999). Even though higher doses were prescribed, 14.1% still had Cmin
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