Aim: To evaluate drug–drug interaction (DDI) between tacrolimus (TAC) and different formulations of voriconazole (VRCZ) in adults and pediatrics with different ages. Method: Physiologically based pharmacokinetics (PBPK) models were used to evaluate DDI between oral TAC and different formulations of VRCZ (oral and intravenous (IV) formulations) in adults and pediatrics with different age groups. Both single dose and multiple dose administration were assessed. Multiple dosage regimens were maintained for 7 days. Result: A higher IV dose might lead to a great increase in area under the plasma concentration-time curve (AUC) and maximum concentrations (Cmax) of TAC in both adults and pediatrics. Besides, compared with IV administration, these two PK values of TAC increased more when combined with VRCZ orally. The ratio of two PK values increased with the age growth in pediatrics. And it increased progressively to adult values at the age of 3-8 years. Tacrolimus liposolubility was the most significant parameter on the DDI between TAC and VRCZ. Conclusion: In pediatric population, VRCZ had a less impact on PK of TAC than that in adults. The DDI progressed gradually as the age advances in pediatrics and finally equal to adults. Oral VRCZ increased PK parameters of tacrolimus even more than IV administration. Personalized dosage adjustment should be considered in clinical practice when co-administrated with VRCZ, especially in adults or in oral formulation.

Mucormycosis was an acute and invasive fungal infection with a high mortality rate. The treatment of mucormycosis was challenging. And the incidence of the mucormycosis seems to be increasing. The key to Mucormycosis therapy not only depend on anti-Mucor infection, but also included the management of some risk factors. Liposomal amphotericin B (L-AMB) was the first line drug to treat mucormycosis. The dosage regimen recommended by the guideline was often associated with higher nephrotoxicity and morbidity. A pharmacokinetic/pharmacodynamic (PKPD) model was conducted to evaluate suitable dosage regimens in Mucormycosis patients. 10mg/kg/day LAMB recommended in the guidelines might not be needed. 5mg/kg/day LAMB might be sufficient to achieve the target value of PKPD and indicated a good anti-Mucor effect. Successful management of mucormycosis was also based on suitable management of several risk factors which played a very important role in the progression of mucormycosis, such as iron factor, diabetes mellitus with acidosis and thrombosis. Application of deferasirox, statins and keep platelet level might be promising approaches in mucormycosis therapy.

Objective: To assess whether dose adjustments of linezolid were needed based on renal function and body weight against methicillin-resistant Staphylococcus aureus (MRSA) infections. Methods: Monte Carlo simulations (MCSs) were conducted to simulate pharmacokinetic/pharmacodynamic (PKPD) model. Area under the concentration time curve (AUC)/ minimum inhibitory concentration (MIC) ratio and percentage of time above the MIC (%T>MIC) were regarded as PKPD targets. The probability of target attainment (PTA) and cumulative fractions of response (CFR) were calculated to assess the efficacy. Regarding safety, trough plasma concentration (Cmin) > 8 mg/L was used to target for toxicity. Results: Using AUC /MIC > 100 as the parameter, the CFR of linezolid at the standard dose [600 mg every 12 h (q12h)] were 57.01%, 93.22% and 99.93% in patients with normal renal function, patients with renal dysfunction and low body weight patients with renal dysfunction, respectively. Using 100%T > MIC as the parameter, all the CFR of three population groups were more than 90% at the standard dose. The percentages of Cmin > 8 mg/L at the standard dose of linezolid were 24.16%, 53.24% and 90.10% in three population groups on day 7. Conclusions: The risk of thrombocytopenia of linezolid was extremely high in low body weight patients with renal impairment when receiving standard linezolid dose. 600 mg q12h might be effective and safe against MRSA infection in patients with normal renal function, while 450mg q12h and 300mg q12h in patients with renal dysfunction and low body weight patients with renal dysfunction, respectively.