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Start Over Author "Ran, Ran" Publisher elsevier b.v.
365 results on '"Ran, Ran"'

49. Plasma Protein Binding Determination for Unstable Ester Prodrugs: Remdesivir and Tenofovir Alafenamide.

Author

Wen, Anita, Qin, Ann Ran-Ran, Tarnowski, Thomas, Ling, Kah Hiing John, Zhang, Haeyoung, Humeniuk, Rita, Regan, Sean, Saquing, Jovita, Liu, Wenbin, Venkatarangan, Lata, and Xiao, Deqing

Subjects
*BLOOD proteins, *PROTEIN binding, *REMDESIVIR, *PRODRUGS, *TENOFOVIR, *PLASMA equilibrium
Abstract

• The addition of an organophosphate esterase inhibitor, dichlorvos, stabilized remdesivir (RDV) during equilibrium dialysis for plasma protein binding (PPB) determination. • Dichlorvos did not impact the unbound fraction (f u) of RDV in plasma, and an equilibrium dialysis method for RDV was developed with the addition of dichlorvos. • Tenofovir alafenamide (TAF) was more stable than RDV by a factor of 3 but was not stabilized by dichlorvos. Fit-for-purpose acceptance criteria for equilibrium dialysis (ED) were implemented during PPB method development for TAF. • PPB methods for RDV and TAF were qualified and applied to PPB determinations for clinical studies. Remdesivir (RDV) and tenofovir alafenamide (TAF) are prodrugs designed to be converted to their respective active metabolites. Plasma protein binding (PPB) determination of these prodrugs is important for patients with possible alteration of free fraction of the drugs due to plasma protein changes in renal impairment, hepatic impairment, or pregnancy. However, the prodrugs' instability in human plasma presents a challenge for accurate PPB determination. In this research work, two approaches were used in the method development and qualification for PPB assessment of RDV and TAF. For RDV, dichlorvos was used to inhibit esterase activity to stabilize the prodrug in plasma during equilibrium dialysis (ED). The impact of dichlorvos on protein binding was evaluated and determined to be insignificant by comparing the unbound fraction (f u) determined by the ED method with dichlorvos present and the f u determined by an ultrafiltration method without dichlorvos. In contrast to RDV, TAF degradation in plasma is ∼3-fold slower, and TAF stability cannot be improved by dichlorvos. Fit-for-purpose acceptance criteria for the TAF PPB method were chosen, and an ED method was developed based on these criteria. These two methods were then qualified and applied for PPB determinations in clinical studies. [ABSTRACT FROM AUTHOR]

Published
2023
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50. Effect of Ketorolac Tromethamine Combined With Remifentanil on Reducing Complications During the General Anesthesia Emergence.

Author

Zhang, Xi, Chang, Jie, Ran, Ran, Xiao, Yun, Cao, Hong, and Wang, Yuqi

Abstract

To observe the effect of ketorolac tromethamine combined with remifentanil in sedation and analgesia during general anesthesia emergence and reducing general anesthesia complications. This is an experimental design. A total of 90 patients who underwent partial or total thyroidectomy in our hospital were selected and randomly divided into three groups with 30 cases in each group. Routine general anesthesia combined with endotracheal intubation was given for general anesthesia, and different treatments were administered when the skin was sutured. Group K: intravenous injection of ketorolac tromethamine 0.9 mg/kg, intravenous injection of normal saline 10 mL/h by micropump until awakening and extubation; R group: intravenous injection of normal saline 2 mL, micropump intravenous injection of remifentanil 0.1 mcg/kg/min until awakening and extubation; KR group: intravenous injection of ketorolac tromethamine 0.5 mg/kg, micropump intravenous injection remifentanil 0.05 mcg/kg/min until awakening and extubation. After the operation, all patients entered the postanesthesia care unit (PACU) for recovery, extubation, scoring. The incidence and condition of various complications were counted. There was no significant difference in the general information or operation duration of the patients (P >.05). The types of general anesthesia induction drugs in each group were the same, and there was no significant difference in drug measurement (P >.05). The visual analogue scales of KR group were: 2.2 ± 0.6(T0) and 2.4 ± 0.9(T1), the Self-Rating Anxiety Scale scores of the KR groups were: 4.1 ± 0.6(T0), 3.7 ± 0.4(T1). Compared with the KR group, the visual analogue scale and Self-Rating Anxiety Scale scores of the K and R groups at T0 and T1 were increased (P <.05); the visual analogue scale and Self-Rating Anxiety Scale scores of the K and R groups at T0 and T1 were not significantly different (P >.05); at T2, there was no significant difference in visual analogue scale and Self-Rating Anxiety Scale scores among the three groups (P >.05). There was no significant difference in extubation time or PACU transfer time among the three groups (P >.05). The incidence of adverse reactions in KR group were: 3.3% (nausea), 3.3% (vomit), 0 (coughing and drowsiness). Compared with the KR group, the incidence of adverse reactions was higher in the K and R groups. Ketorolac tromethamine combined with remifentanil can effectively relieve pain and sedation during general anesthesia recovery and reduce the incidence of complications related to general anesthesia recovery. At the same time, the application of ketorolac tromethamine can reduce the dosage of remifentanil and inhibit the occurrence of adverse reactions when used alone. [ABSTRACT FROM AUTHOR]

Published
2023
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