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The pharmacokinetics of teicoplanin differs in children as compared with adults, and especially in renally impaired pediatric patients. Inappropriate empirical antibacterial therapy may lead to treatment‐related antibacterial resistance and increased toxicity, making adjustment of the dosage regimen essential. In the present study, physiologically based pharmacokinetic (PBPK) models were developed to define the appropriate dosage regimen for pediatric patients with differing renal function. Our PBPK models accurately predicted teicoplanin exposures in both adult and pediatric subjects after single and multiple intravenous infusions, with a <1.36‐fold error between predicted and observed data, and all observed data were within minimal and maximal data of the corresponding population simulation. The area under the plasma concentration–time curve was predicted to increase 1.25‐fold, 1.95‐fold, and 2.82‐fold in pediatric patients with mild, moderate, and severe renal impairment, respectively, relative to that of healthy children. Subsequently, the results of Monte Carlo simulations indicated that the recommended dosing of 12, 9.5, 6, and 4 mg/kg at 12‐hour intervals would be appropriate in pediatric patients with normal renal function and in those with mild, moderate, and severe renal impairment, respectively, at a susceptible minimum inhibitory concentration <2 mg/L. In conclusion, our PBPK model with an incorporated Monte Carlo simulation can provide improved guidance on dosing in pediatric patients with differing renal function and provide a basis for precision therapy with teicoplanin. [ABSTRACT FROM AUTHOR]

Ceftaroline fosamil is a fifth‐generation cephalosporin approved as a treatment for adults and children with community‐acquired bacterial pneumonia and acute bacterial skin and skin structure infections. However, its pharmacokinetics have not been fully evaluated in children with renal impairment. This study aimed to propose proper ceftaroline dosages optimized for the renally impaired pediatric population using physiologically based pharmacokinetic (PBPK) modeling. A PBPK model of ceftaroline was established and verified to simulate its disposition in the healthy population and renally impaired adults and to predict the exposure in renally impaired pediatric patients. Consistency was confirmed between simulated and observed data after intravenous administration of various ceftaroline regimens; fold errors were within the 2‐fold error range. Among 6‐year‐old children, healthy subjects had 1.5‐fold, 2‐fold, and 2.6‐fold lower areas under the plasma concentration–time curve (AUCs) than the moderate, severe, and end‐stage renally impaired patient groups, respectively; among 1‐year‐old children, healthy subjects had 1.5‐fold, 2.1‐fold, and 2.5‐fold lower AUCs than the respective renally impaired patient groups; among 1‐month‐old children, healthy subjects had 1.5‐fold, 1.8‐fold, and 2.2‐fold lower AUCs than the respective renally impaired patient groups. The proposed dosage should be adjusted to 8, 6, and 5 mg/kg every 8 hours for patients aged ≥2 years to <18 years (≤33 kg) with moderate, severe, and end‐stage renal impairment, respectively; 5, 4, and 3 mg/kg every 8 hours for patients aged 2 months to <2 years with moderate, severe, and end‐stage renal impairment, respectively; 4, 3.5, and 2.5 mg/kg every 8 hours for patients 0 to <2 months of age with moderate, severe, and end‐stage renal impairment, respectively. Furthermore, pharmacodynamic investigations demonstrated that adequate antimicrobial effects were attained at the proposed doses in 3 age groups. Hence, our PBPK model can be an effective tool to support ceftaroline dosage proposals for renally impaired pediatric patients. [ABSTRACT FROM AUTHOR]

Pramipexole is the first‐line medication recommended by the British National Institute for Health and Care Excellence. Pramipexole is predominantly eliminated by renal excretion. The aim was to develop a physiologically based pharmacokinetic (PBPK) model of pramipexole, providing a basis for its individualized administration. The role of glomerular filtration and organic cation transporter 2 (OCT2) in renal tubular secretion was considered. Plasma concentration‐time profiles of pramipexole were predicted and validated, first in healthy populations and then in PD patients with varied renal function. Finally, the pharmacokinetics of PD patients with different degrees of renal impairment were predicted. The simulated pharmacokinetic parameters, including maximum plasma concentration (Cmax), area under the plasma concentration‐time curve (AUC), time to maximum plasma concentration (tmax), and steady‐state trough plasma concentration values, obtained using the PBPK model were validated using fold error values, which were all smaller than 2. The successfully validated model supported that OCT2‐mediated tubular secretion was affected proportionally to changes in glomerular filtration for various degrees of renal impairment. The predicted AUC0‐inf values were increased 1.16‐, 1.76‐, 3.26‐, and 9.48‐fold in mild, moderate, and severe renal impairment and end‐stage renal disease (ESRD) subjects, resepctively, compared with PD patients with normal renal function. It appears that PD patients with mild renal impairment are unlikely to require dose adjustment (0.125 mg 3 times a day). The pramipexole dose should be reduced to approximately 0.125 mg twice daily, 0.125 mg once daily, and 0.0375 mg once daily in PD patients with moderate renal impairment, severe renal impairment, and ESRD, respectively. [ABSTRACT FROM AUTHOR]