Abstract We compared the predictive accuracy of TEIC concentrations (TEIC _conc ) calculated using either serum cystatin C (CysC) or serum creatinine (SCr) and the population mean method using the ...mean population parameter of TEIC _conc for Japan. We also compared the predicted TEIC _conc to measured TEIC _conc . Creatinine clearance (CLCr) predicted using the Cockcroft–Gault (C&G) equation with SCr was 45.23 mL/min (interquartile range IQR: 32.12–58.28), and the glomerular filtration rate (GFR) predicted using the Hoek equation with CysC was 45.23 mL/min (IQR: 35.40–53.79). The root mean-squared prediction error (IQR) based on CLCr predicted using the C&G equation with SCr was 6.88 (3.80–9.96) μg/mL, and that based on GFR predicted using the Hoek equation with CysC was 6.72 (3.77–9.68) μg/mL. Predicted TEIC _conc did not differ significantly between the two methods. The predictive accuracy of the TEIC _conc using the Hoek equation with CysC was similar to that of CLCr using the C&G equation with SCr. These findings suggest that the predictive accuracy of the TEIC _conc using CLCr based on the G&G equation and SCr might be sufficient for the initial dose adjustment of TEIC. Given that we were unable to confirm that CysC is the optimal method for predicting TEIC _conc , the expensive measurement of CysC might not be necessary.
This study investigated endogenous factors that may increase the elimination of vancomycin (VCM) in adult methicillin-resistant Staphylococcus aureus (MRSA) patients with pneumonia.
48 patients (32 ...men and 16 women) admitted to the National Hospital Organization Kumamoto Medical Center for pneumonia due to MRSA were evaluated. VCM (500 - 2,000 mg/dose) was administered intravenously for 60 - 120 min at 8- - 12-h intervals. The dose of VCM prescribed was determined based on the treatment guidelines of the Infectious Diseases Society of America and was dependent on a patient's creatinine clearance.
Univariate analysis identified that potassium value (K) (p = 0.081) and urinary pH (p = 0.026) were possibly associated with decreased VCM concentration. Multivariate analysis confirmed that urinary pH was an independent risk factor for VCM clearance (p = 0.029). VCM clearance in patients with a urine pH of 8 was significantly higher (p = 0.032) than in patients with a urinary pH of 5. As urinary pH increased in alkalinity, a greater decrease in VCM concentrations was observed.
Elevation of urinary pH promotes the urinary excretion of VCM, likely by promoting the dissociation of the carboxyl group of VCM. Thus, in the clinical setting, urinary pH should be measured and considered when determining dosage, as it may affect the VCM blood concentration.
What is known and objective
We investigated the elimination efficiency and pharmacokinetics (PK) parameters of vancomycin (VCM) in patients undergoing continuous haemodiafiltration (CHDF) using a ...polyethyleneimine‐coated polyacrylonitrile membrane (AN69ST) for dosage adjustment.
Methods
We conducted a retrospective study of CHDF patients treated with VCM from December 2017 to August 2019. We calculated PK parameters of VCM and determined the 24‐hour dose required to maintain the target trough concentration of VCM (VCM_trough).
Results and discussion
The average (95% CI) volume of distribution and total clearance of VCM were 75.5 L (63.7‐87.3 L) and 1.84 L/h (1.38‐2.30 L/h), respectively, and the elimination rate constant and half‐life were 0.026/h (0.017‐0.034/h) and 31.2 h (22.8‐39.5 h), respectively. The average AN69ST clearance of VCM (CL_CHDF) was 0.69 L/h (0.52‐0.86 L/h). The estimated average doses required to maintain VCM_trough of 10, 15 and 20 μg/mL were 623.1 mg (379.8‐866.4 mg), 934.6 mg (569.7‐1299.5 mg) and 1246.2 mg (759.6‐1732.8 mg), respectively.
What is new and conclusion
The PK of VCM and CL_CHDF of AN69ST were clarified. These results suggest that it is possible to adjust the dose of VCM in using AN69ST, which efficiently removes cytokines, and contributes to improvement of serious infections.
This study showed pharmacokinetics of vancomycin in patients undergoing CHDF using AN69ST and estimated the 24‐hour dose required to maintain the target trough concentration of vancomycin.
We administered FOLFOX (oxaliplatin (L-OHP) plus infusional 5-fluorouracil (5-FU) and leucovorin) to an hemodialysis (HD) patient with advanced gastric cancer (AGC), and investigated pharmacokinetics ...(PKs) and dialyzability of L-OHP. The patient was a 54-year-old Japanese man with a diagnosis of inoperable AGC. FOLFOX was instituted 3 h prior to the start of a 4 h HD period with the L-OHP and 5-FU doses reduced by 50% for the first cycle, and 30% reduced dose was administered for the second cycle. We performed an analysis of the PKs of L-OHP during these two cycles. Volume of distribution and area under the curve of the 30% reduced L-OHP dose were 56.7 L and 30.0 μg·h/mL, respectively. A dose reduction of L-OHP by 30%-50% may be advisable for the initial administration, given the need for careful administration of chemotherapy in HD patients, with particular attention to the development of hematological toxicities and neuropathy.
A dense and uniform apatite layer about 20μm thick was formed on a poly(ether sulphone) (PESF) substrate treated with glow discharge in O
2 gas by a biomimetic process. The apatite-polymer composite ...obtained was implanted into a rabbit tibia and the structure of the PESF-apatite-bone interface was observed under a scanning and a transmission electron microscope 8 weeks after implantation. The apatite layer formed by the biomimetic process was confirmed to consist of small crystals of apatite with a structure similar to that of apatite in bone. The apatite layer remained on the substrate in the body, and bonded to the apatite in the bone directly. This type of apatite-organic polymer composite expected to be useful as bone-repairing material.
Herein, we investigated the pharmacokinetic (PK) profile of nedaplatin (cis-diamine-glycolateplatinum; CDGP) in a hemodialysis (HD) patient with advanced esophageal squamous cell carcinoma (ESCC) by ...administering the CDGP immediately prior to HD. Our patient was treated with CDGP (45 mg/m2 for a total dose of 60.2 mg) and 5-fluorouracil (560 mg/m2 for a total dose of 750 mg) before initiating HD. The total platinum (Pt) concentration (Pt_total) and free Pt concentration (Pt_free) 2 h after completion of HD were 0.4 μg/mL and 0.3 μg/mL, respectively. The removal rates of Pt_total and Pt_free by the dialyzer were 76.5% and 84.6%, respectively. Twenty-four hours after CDGP administration, the Pt_free was below the detection limit of the method of analysis. Pt_free within the range of the recommended CDGP target AUC0-24 was 8-10 μg/mL•h, the AUC0-24 of Pt_total and Pt_free were 16.5 μg/mL•h and 8.8 μg/mL•h, respectively. We conclude that HD should be performed after the end of CDGP infusion as part of the CDGP chemotherapy regimen for HD patients with ESCC, and suggest that HD is effective for obtaining a PK profile of CDGP similar to patients with normal renal function.
Falls are common in elderly patients and are often serious. Several drugs have been associated with an increased risk of fall. Older adults often take multiple drugs for chronic diseases, and thus ...may be at increased risk from drugs associated with fall. We investigated the association between drug use and falling in hospitalized older people, with the goal of identifying medications that may increase the risk of a fall. A retrospective case control study was performed at the National Hospital Organization Kumamoto Saishunso Hospital in Japan. Medications taken by patients who fell (n=57) were compared with those taken by patients who did not fall (n=63). The median age (interquartile range; IQR) of the fall and non-fall groups were 75.0 (67.0-83.0) and 80.0 (70.3-84.5) years, respectively. The characteristics of the two groups were similar, with no significant differences in age, sex, or body weight. The probability of falling increased when the patients used zolpidem odds ratio (OR)=2.47; 95%CI: 1.09-5.63; p<0.05 and calcium channel antagonists (OR=0.299; 95%CI: 0.13-0.68; p<0.01), and was also related to physical factors (OR=2.27; 95%CI: 1.01-5.09; p<0.05). Elderly patients taking zolpidem may fall due to sleepiness, and blood pressure control may be important to prevent orthostatic high blood pressure. In the treatment of elderly people, medical staff should try to choose drugs that prevent fall or are not associated with falling.
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