Purpose: Intrathecal morphine infusion therapy via a percutaneous port (IMITPP) has been used widely for its relatively low initial cost. However, there is scarce knowledge about IMITPP. In this study, we sought to evaluate efficacy, complications, and the interval required to achieve the cost equivalence of IMITPP in patients with refractory cancer pain in China. Patients and Methods: A retrospective chart review was conducted on cancer patients who had received IMITPP at our hospital between April 2017 and April 2019. Data from the numeric pain rating scale and Karnofsky performance scores, and complications and costs related to IMITPP were collected from medical records. Daily analgesic costs before and after IMITPP were calculated based on the doses of opioids on admission and at discharge, respectively. The doses of systemic opioids before IMITPP were stratified into very high doses [VHD, oral morphine equivalent dose (OMED) >599 mg/day], high doses (HD, 300 mg/day ≤ OMED ≤ 599 mg/day), and regular doses (RD, OMED < 300 mg/day). Results: Intrathecal morphine infusion therapy via a percutaneous port provided significant pain relief, but impaired activities of daily living in patients with refractory cancer pain. The commonly reported complications included nausea/vomiting and urinary retention, most of which were managed with symptomatic therapies. The median interval required to achieve cost equivalence was 11.44 months. The median intervals of VHD group and HD group were significantly shorter than that of RD group. Conclusion: Intrathecal morphine infusion therapy via a percutaneous port provided effective cancer pain management without causing serious complications. Patients with higher doses of systemic opioids would economically benefit from IMITPP in a shorter time.

Summary Mycophenolate mofetil (MMF) is used to prevent acute rejection following solid organ transplantation in transplant centers all over the world. Patients from different ethnic backgrounds are treated with this drug, for which therapeutic drug monitoring (TDM) has not become the standard of practice in most centers. Whether or not some ethnic groups require a different MMF dose has been a topic of debate in recent years. In this review, it is shown that Asian patients, compared with Caucasian patients, with a comparable MMF dose reach higher mycophenolic acid (MPA) exposure. Also clinical experience points toward more adverse events in case of treatment with 1 g MMF bid in Asian patients, and therefore, for this ethnic group, a lower maintenance dose seems justified. In contrast, African American patients reach similar drug concentrations as Caucasians patients receiving the same MMF dose, but due to immunological reasons, they require a higher MMF dose to reach comparable acute rejection incidences. When TDM is performed, clinicians can correct the dose and compensate for interethnic differences in drug exposure. Otherwise, it is important to choose the right dose. This optimal dose is 20–46% lower in Asian transplant recipients than in Caucasian or African American patients.

Rivaroxaban is a popular direct factor Xa inhibitor used for anticoagulation therapy in patients with nonvalvular atrial fibrillation (NVAF). The aim of this study was to establish a population pharmacokinetic (PPK) model for rivaroxaban in elderly Chinese patients with nonvalvular atrial fibrillation, evaluate precision dosing regimens, and analyze hemorrhagic risk after rivaroxaban treatment. A 1-compartment population PK model with estimated glomerular filtration rate (eGFR), total bilirubin (TBIL), and ABCB1 rs1045642 as major covariates for apparent clearance was developed using the nonlinear mixed-effects model (NONMEM). A Monte Carlo simulation was performed to evaluate various dosing schemes and different levels of covariates for the target range of therapeutic drug-monitoring concentrations (C max,ss and C min,ss ). The exposure to rivaroxaban was simulated and assessed through hemorrhagic risk evaluation. The results showed that the average probability of target attainment (PTA) for optimal dosing regimens with different covariate levels for the targeted C max,ss and C min,ss were 29.35% to 31.3% and 64.91% to 65.8%, respectively. A dosage of 10 mg of rivaroxaban in elderly Chinese patients with normal renal and liver function was appropriate. The area under the concentration-time curve estimated over 24 hours with precision dosing at steady state (AUC 24,ss ) was statistically significantly associated with an increased risk of bleeding events (OR 1.0006, 95%CI 1.0003 to 1.001, P < .0001), and the bleeding risk increased by 1.82-fold for every 1000 μg*h/L increase in AUC 24,ss . A lower dose is recommended for elderly patients with renal impairment to avoid overexposure and bleeding events. The PPK model could inform individualized dosing for elderly Chinese patients with nonvalvular atrial fibrillation receiving rivaroxaban anticoagulation therapy.

Background: The anti-CD20 antibody rituximab, which promotes the selective depletion of CD20 positive B cells, was the first targeted therapy that was approved for the treatment of B-cell malignancies, and it is now widely prescribed in both malignant and non-malignant, immune-related diseases. However, the cause of its various clinical responses in certain diseases, have not been clearly elucidated. The variabilities in inter-individual pharmacokinetic and the emerging evidence of the relationships between pharmacokinetic and pharmacodynamic may provide a better understanding of this drug. Methods: We searched and summarized the latest published articles on rituximab pharmacokinetic profiles and the pharmacokinetic/pharmacodynamic models in different patient populations, including B-cell malignancies, rheumatoid arthritis, ANCA-associated vasculitis, and glomerular kidney diseases. Results: Most pharmacokinetic data are drawn from clinical studies in oncology clinical practice. Body weight, gender, and antigen-related factors are proven to be the key factors affecting rituximab pharmacokinetics. In addition, the positive exposure-response relations were reported, which provides encouraging evidence for individualized therapies. While in immune disorders, especially in the off-labeled indications, pharmacokinetic studies are quite limited. Compared with that in B-cell malignancies, the differences in the pharmacokinetic parameters may be attributed to the different pathogeneses of diseases, mechanisms of action and dosing strategies. However, the correlation between drug exposure and clinical outcomes remains unclear. Conclusion: Here we provide an overview of the complexities associated with rituximab pharmacokinetics and pharmacodynamics in different diseases. Although many influencing factors need to be verified in future studies, a better understanding of the relationships between pharmacokinetic and pharmacodynamic may assist in optimizing rituximab clinical practice.