Population Pharmacokinetics
Scott Patterson, Byron Jones in Bioequivalence and Statistics in Clinical Pharmacology, 2017
Severity of liver disease is typically measured by the Child–Pugh score [374], and subsequently categorized as healthy, mild, moderate, or severe liver function impairment, depending on the extent of damage to the liver and impairment of its function. If a drug is eliminated (in the ADME sense) by metabolism or excretion (into bile) in the liver, the drug would be expected to accumulate in the plasma. Decreased clearance of drug by the liver [30] implies increased AUC and Cmax, and, as these increase the likelihood of adverse events associated with exposure (relative to the NOAEL), would also be expected to increase. Therefore, it is important to understand the magnitude of increased exposure in patients with impaired hepatic function to determine [30] if it is necessary to reduce the dose in such patients or potentially to contraindicate the use of the drug.
Development of palliative medicine in the United Kingdom and Ireland
Eduardo Bruera, Irene Higginson, Charles F von Gunten, Tatsuya Morita in Textbook of Palliative Medicine and Supportive Care, 2015
Prognostic indicators that are additively negative in endstage cirrhosis are laboratory indicators of severely altered liver functionality and several clinical conditions (treatment-refractory ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, hepatic encephalopathy refractory to therapies, recurrent variceal bleeding) 69*. Other factors have also been reported, including malnutrition, muscle wasting, active alcoholism, hepatocellular carcinoma, and HBsAg positivity [12]. The two most widely used prognostic models developed for decompensated cirrhosis are the Child-Pugh score and the model for end-stage liver disease (MELD) 70***,97,98*. A prognosis of less than 6 months is estimated for a Child-Pugh score of ≥12 or a MELD score of ≥21[99]. A 2006 review by Cholongitas et al. reported that general ICU models, that is, acute physiology and chronic health evaluation (APACHE), organ system failure (OSF), and sequential organ failure assessment (SOFA) 100,101***, showed a better performance in cirrhotic populations compared to that of scores designed specifically for the disease 102*,103***.
Echinocandins for prevention and treatment of invasive fungal infections
Mahmoud A. Ghannoum, John R. Perfect in Antifungal Therapy, 2019
Hepatic insufficiency appears to reduce elimination of caspofungin and micafungin, while plasma concentrations of anidulafungin are decreased in those with severe hepatic impairment receiving anidulafungin [5,92]. Dose reduction should be considered when administering caspofungin to patients with moderate hepatic insufficiency [5]. In a single dose study of 70 mg, those with Child Pugh scores of 5–6 experienced an increase in AUC of 55% compared to historical healthy controls, while those with Child Pugh scores of 7–9 experienced a mean AUC increase of 76% [63]. These differences were not as pronounced with daily caspofungin doses of 50 mg, where subjects with mild hepatic insufficiency experienced increases in AUC of approximately 19%–25% compared to healthy controls. In this study, subjects with moderate hepatic impairment received 35 mg daily, following the 70 mg loading dose. Patients with severe liver dysfunction (Child Pugh score >9) were excluded from clinical trials with caspofungin, so there is limited clinical experience with the drug in this severely ill patient population.
Improvement of human platelet aggregation post-splenectomy with paraesophagogastric devascularization in chronic hepatitis B patients with cirrhotic hypersplenism
Published in Platelets, 2020
Hui Zhang, Shaoying Zhang, Jian Zhang, Rui Zhou, Yongzhan Nie, Song Ren, Jun Li, Keping Feng, Fanpu Ji, Guangyao Kong, Zongfang Li
Cirrhotic patients can be classified according to Child-Pugh score, as grade A (5 or 6), B (7–9) or C (10–15). This scoring system was first proposed by Child and Turcotte, and later modified by Pugh et al [18]. The main parameters of the now aptly named Child–Pugh score include the features of hepatic encephalopathy, ascites, prothrombin time (seconds prolonged) or international normalized ratio, and concentrations of serum total bilirubin and albumin. It has been widely used to assess the severity of liver dysfunction in clinical work [18–20]. Splenomegaly and hypersplenism are common in cirrhotic patients. However, the severity of hypersplenism is not directly related to the size of the spleen nor the severity of the PH. Splenectomy is very effective in resolving hypersplenism and has been the standard approach for treatment [6,21]. A more obvious increase in PLT counts can be expected after the splenectomy in cases of severe thrombocytopenia, due to the larger spleen size (indicative of more PLTs stored) and higher phagocytic capacity of splenic macrophages (since peripheral PLT destruction is a major cause of thrombocytopenia) [22].
Clinical value of hemodynamic changes in diagnosis of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt
Published in Scandinavian Journal of Gastroenterology, 2022
Wanyan Li, Yayang Duan, Zhike Liu, Xiaofeng Lu, Jingwen She, Jing Qing, Chaoxue Zhang
Patients who underwent TIPS interventional treatment of cirrhotic portal hypertension in The First Affiliated Hospital of Anhui Medical University from January 2018 to January 2021 were studied. A total of 73 patients met the selection criteria. Among them, 51 patients who did not develop HE within 3 months after the operation comprised the control group (9 males and 12 females aged 29–75 with an average age of 56.06 ± 11.49); 22 patients who developed HE within 3 months after the operation comprised the observation group (16 males and 6 females aged 41–74 with an average age of 59.05 ± 11.64). All patients underwent blood routine, liver and kidney function, blood ammonia and routine color Doppler ultrasound tests before TIPS operation, as well as within 24 h and 3 months after the operation. These tests would be stopped when the 3-month follow-up ended, or patients developed HE within the follow-up. The HE was scored with the Delirium Rating Scale. The Child–Pugh score is a comprehensive scoring system based on serum bilirubin, albumin, prothrombin time, degree of ascites and HE. A Child–Pugh score of 5–6 is considered as grade A, 7–9 is grade B, and 10–15 is grade C.
Circulating glucagon-like peptide-1 level in patients with liver cirrhosis
Published in Archives of Physiology and Biochemistry, 2023
Masoud Nouri-Vaskeh, Neda Khalili, Amirreza Khalaji, Pouya Behnam, Leila Alizadeh, Sara Ebrahimi, Neda Gilani, Mehdi Mohammadi, Seyed Alisalar Madinehzadeh, Mohammad Zarei
Blood samples (5 cc) were collected after at least 9 h overnight fasting from the participants in EDTA tubes, centrifuged at 1600 spins for 15 min, and then kept at −70 °C for further analysis. Fasting blood glucose (FBG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALK), sodium (Na), potassium (K), creatinine (Cr), blood urea nitrogen (BUN), prothrombin time (PT), international normalised ratio (INR), total bilirubin, and plasma albumin were measured by using commercial kits. An enzyme-linked immune sorbent assay (ELISA) was used for the estimation of fasting GLP-1 plasma levels (RAB0201; Sigma-Aldrich, MO, USA). The minimum detectable concentration of GLP-1 assay was 1.17 pg/mL. Child-Pugh score was measured based on the patients’ clinical and laboratory data (total bilirubin, plasma albumin, INR, ascites, and hepatic encephalopathy), and the MELD score was measured based on the patients’ laboratory data (Cr, Na, total bilirubin, and INR). Scores were calculated using the MDCalc medical calculator application (MD Aware, LLC, New York, NY).
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