Klirens lidokaina kao farmakokinetički parametar metaboličke aktivnosti kod pacijenata sa oštećenjem jetre

Background: The study aimed to estimate lidocaine (LID) pharmacokinetic parameter values in patients with impaired liver function, level of correlation between the pharmacokinetic parameters and Child-Pugh class and change in pharmacokinetic parameters after liver tumor resection compared to the preoperative value. Methods: Patients with impaired liver function were subject to the LID test 1 day prior to, 3 and 7 days after the inter- vention. LID was administered in single i.v. dose of 1 mg/kg. Blood samples were collected at 15, 30 and 90 minutes after drug administration. Non-compartmental analysis was applied for calculating the pharmacokinetic parameters. Results: The study included 17 patients with the diagnosis of cirrhosis and 41 patients with liver tumor. In both groups of patients, the values of the coefficients of correlation show the best correlation between clearance (CL) and Child-Pugh score (-0.693, p<0.005) over other pharmacokinetic parameters. The results indicate worsening hepatic function on 3rd day after operation in comparison to the values of LID CL prior to operation (mean LID CL for patients with Child-Pugh class A are 25.91 L/h, 41.59 L/h, respectively; while for B class are 16.89 L/h, 22.65 L/h, respectively). On day 7th, the values of LID CL (mean value for patients with Child-Pugh class A and B are 40.98 L/h and 21.46 L/h, respectively) are increased in comparison to 3rd day after. Conclusions: LID pharmacokinetic parameters consequent- ly changed according to the severity of liver impairment, assessed by Child-Pugh score. Values of LID CL and vol- ume of distribution (Vd) coupled with standard biochemical parameters may be used for preoperative assessment of liver function and monitoring of its postoperative recovery.Uvod: Cilj studije bila je procena vrednosti farmako- kinetičkih parametara lidokaina (LID) kod pacijenata sa oštećenom funkcijom jetre, stepena korelacije izme|u farmakokinetičkih parametara i Child-Pugh klase i promene farmakokinetičkih parametara posle resekcije tumora jetre u odnosu na preoperativnu vrednost. Metode: Pacijenti sa o{te}enom funkcijom jetre bili su podvrgnuti LID testu 1 dan pre, 3. i 7. dana nakon intervencije. LID je primenjen u pojedinačnoj i.v. dozi od 1 mg/kg. Uzorci krvi su sakupljeni 15, 30 i 90 minuta nakon primene leka. Za izračunavanje farmakokinetičkih parametara primenjena je neprostorna analiza. Rezultati: Studijom je obuhvaćeno 17 pacijenata sa dijagnozom ciroze i 41 pacijent sa tumorom jetre. Kod obe grupe pacijenata, vrednosti koeficijenata korelacije pokazuju najbolju korelaciju izme|u klirensa LID (CL) i Child-Pugh skora (-0,693, p<0,005) u odnosu na ostale farmakokinetičke parametre. Rezultati ukazuju na pogoršanje funkcije jetre 3. dana nakon operacije u pore|enju sa vrednostima LID CL pre operacije (srednje vrednosti LID CL kod pacijenata Child-Pugh grupe A iznosile su 25,91 L/h, 41,59 L/h, respektivno; dok su kod pacijenata u klasi B iznosile 16,89 L/h, 22,65 L/h, respektivno). Sedmog dana vrednosti LID CL (srednja vrednost u Child-Pugh grupi A i B iznosile su 40,98 L/h i 21,46 L/h, respektivno) bile su veće u odnosu na 3. dan posle hirur{ke intervencije. Zaključak: Farmakokinetički parametri LID se razlikuju u zavisnosti od težine oštećenja jetre, procenjenih Child-Pugh skorom. Vrednosti farmakokinetičkih parametara LID u kombinaciji sa standardnim biohemijskim parametrima mogu se koristiti za preoperativnu procenu funkcije jetre i praćenje njenog postoperativnog oporavk

Lidocaine clearance as pharmacokinetic parameter of metabolic hepatic activity in patients with impaired liver

Background: The study aimed to estimate lidocaine (LID) pharmacokinetic parameter values in patients with impaired liver function, level of correlation between the pharmacokinetic parameters and Child-Pugh class and change in pharmacokinetic parameters after liver tumor resection compared to the preoperative value. Methods: Patients with impaired liver function were subject to the LID test 1 day prior to, 3 and 7 days after the intervention. LID was administered in single i.v. dose of 1 mg/kg. Blood samples were collected at 15, 30 and 90 minutes after drug administration. Non-compartmental analysis was applied for calculating the pharmacokinetic parameters. Results: The study included 17 patients with the diagnosis of cirrhosis and 41 patients with liver tumor. In both groups of patients, the values of the coefficients of correlation show the best correlation between clearance (CL) and Child-Pugh score (-0.693, p<0.005) over other pharmacokinetic parameters. The results indicate worsening hepatic function on 3rd day after operation in comparison to the values of LID CL prior to operation (mean LID CL for patients with Child-Pugh class A are 25.91 L/h, 41.59 L/h, respectively; while for B class are 16.89 L/h, 22.65 L/h, respectively). On day 7th, the values of LID CL (mean value for patients with Child-Pugh class A and B are 40.98 L/h and 21.46 L/h, respectively) are increased in comparison to 3rd day after. Conclusions: LID pharmacokinetic parameters consequently changed according to the severity of liver impairment, assessed by Child-Pugh score. Values of LID CL and volume of distribution (Vd) coupled with standard biochemical parameters may be used for preoperative assessment of liver function and monitoring of its postoperative recovery

Genetic determinants of response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer identified by whole exome sequencing

The cornerstone in the treatment of locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision. Reliable predictors of response to nCRT in LARC remain an unmet need in colorectal cancer research. This study used high throughput DNA analysis to investigate genetic differences between highly responsive tumors and tumors resistant to nCRT.European Human Genetics Conference Hybrid Conference Glasgow, Scotland, UK JUNE 10–13, 202