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Monoclonal antibodies are commonly engineered with an introduction of Met428Leu and Asn434Ser, known as the LS mutation, in the fragment crystallizable region to improve pharmacokinetic profiles. The LS mutation delays antibody clearance by enhancing binding affinity to the neonatal fragment crystallizable receptor found on endothelial cells. To characterize the LS mutation for monoclonal antibodies targeting HIV, we compared pharmacokinetic parameters between parental versus LS variants for five pairs of anti-HIV immunoglobin G1 monoclonal antibodies (VRC01/LS/VRC07-523LS, 3BNC117/LS, PGDM1400/LS PGT121/LS, 10-1074/LS), analyzing data from 16 clinical trials of 583 participants without HIV. We described serum concentrations of these monoclonal antibodies following intravenous or subcutaneous administration by an open two-compartment disposition, with first-order elimination from the central compartment using non-linear mixed effects pharmacokinetic models. We compared estimated pharmacokinetic parameters using the targeted maximum likelihood estimation method, accounting for participant differences. We observed lower clearance rate, central volume, and peripheral volume of distribution for all LS variants compared to parental monoclonal antibodies. LS monoclonal antibodies showed several improvements in pharmacokinetic parameters, including increases in the elimination half-life by 2.7- to 4.1-fold, the dose-normalized area-under-the-curve by 4.1- to 9.5-fold, and the predicted concentration at 4 weeks post-administration by 3.4- to 7.6-fold. Results suggest a favorable pharmacokinetic profile of LS variants regardless of HIV epitope specificity. Insights support lower dosages and/or less frequent dosing of LS variants to achieve similar levels of antibody exposure in future clinical applications.

With the aging population, osteoporosis has become an important public health issue. The purpose of this study was to establish a two-compartment model (TCM) to quantify the volumetric bone mineral density (vBMD) of the lumbar spine using abdominal computed tomography (CT) images. The TCM approach uses water as the bone marrow equivalent and K2HPO4 solution as the cortical bone equivalent. A phantom study was performed to evaluate the accuracy of vBMD estimation at 100 kVp and 120 kVp. The data of 180 patients who underwent abdominal CT imaging and dual-energy X-ray absorptiometry (DXA) within one month were retrospectively collected. vBMD of L1–L4 vertebrae were calculated, and the receiver-operating characteristic curve analysis was performed to establish the diagnostic thresholds for osteoporosis and osteopenia in terms of vBMD. The average difference between the measured vBMD following TCM and the theoretical vBMD of the self-made phantom was 0.2%, and the maximum difference was 0.5%. vBMD of lumbar vertebrae obtained from TCM and aBMD obtained by DXA had a significant positive correlation (r = 0.655 to 0.723). The average diagnostic threshold for osteoporosis was 0.116 g/cm3. The sensitivity, specificity, and accuracy were 95.7%, 75.6.5%, and 80.0%, respectively. The average diagnostic threshold for osteopenia was 0.126 g/cm3. The sensitivity, specificity, and accuracy were 81.3%, 82.5%, and 82.7%, respectively. The aforementioned threshold values were used to perform the diagnostics on a test cohort, and the performance was equivalent to that in the experimental cohort. From the perspective of preventive medicine, opportunistic screening of bone mineral density using abdominal CT images and the TCM approach can facilitate early detection of osteoporosis and osteopenia and, with in-time treatment, slow down their progression.

Accurate prediction of blood toxin concentration during and after dialysis will greatly contribute to the determination of dialysis treatment conditions. Conventional models, namely single-compartment model and two-compartment model, have advantages and disadvantages in terms of accuracy and practical application. In this study, we attempted to derive the mathematical model that predicts blood toxin concentrations during and after dialysis, which has both accuracy and practicality. To propose the accurate model, a new two-compartment model was mathematically derived by adapting volume-averaging theory to the mass transfer around peripheral tissues. Subsequently, to propose a practical model for predicting the blood toxin concentration during dialysis, an analytical solution expressed as algebraic expression was derived by adopting variable transformation. Furthermore, the other analytical solution that predicts rebound phenomena after dialysis was also derived through similar steps. The comparisons with the clinical data revealed that the proposed analytical solutions can reproduce the behavior of the measured blood urea concentration during and after dialysis. The analytical solutions proposed as algebraic expressions will allow a doctor to estimate the blood toxin concentration of a patient during and after dialysis. The proposed analytical solutions may be useful to consider the treatment conditions for dialysis, including the rebound phenomenon.

With the aging population, osteoporosis has become an important public health issue. The purpose of this study was to establish a two-compartment model (TCM) to quantify the volumetric bone mineral density (vBMD) of the lumbar spine using abdominal computed tomography (CT) images. The TCM approach uses water as the bone marrow equivalent and K 2 HPO 4 solution as the cortical bone equivalent. A phantom study was performed to evaluate the accuracy of vBMD estimation at 100 kVp and 120 kVp. The data of 180 patients who underwent abdominal CT imaging and dual-energy X-ray absorptiometry (DXA) within one month were retrospectively collected. vBMD of L1-L4 vertebrae were calculated, and the receiver-operating characteristic curve analysis was performed to establish the diagnostic thresholds for osteoporosis and osteopenia in terms of vBMD. The average difference between the measured vBMD following TCM and the theoretical vBMD of the self-made phantom was 0.2%, and the maximum difference was 0.5%. vBMD of lumbar vertebrae obtained from TCM and aBMD obtained by DXA had a significant positive correlation ( r = 0.655 to 0.723). The average diagnostic threshold for osteoporosis was 0.116 g/cm 3 . The sensitivity, specificity, and accuracy were 95.7%, 75.6.5%, and 80.0%, respectively. The average diagnostic threshold for osteopenia was 0.126 g/cm 3 . The sensitivity, specificity, and accuracy were 81.3%, 82.5%, and 82.7%, respectively. The aforementioned threshold values were used to perform the diagnostics on a test cohort, and the performance was equivalent to that in the experimental cohort. From the perspective of preventive medicine, opportunistic screening of bone mineral density using abdominal CT images and the TCM approach can facilitate early detection of osteoporosis and osteopenia and, with in-time treatment, slow down their progression.