Solaiman Ezzafzafi, MD, is a PhD candidate at Amsterdam UMC, affiliated with the Departments of Gastroenterology & Hepatology and Pharmacy & Clinical Pharmacology. His research focuses on alterations in drug pharmacokinetics in liver cirrhosis, with a primary focus on antibiotic pharmacokinetics. Alongside his doctoral research, he is specializing in clinical pharmacology. He has a strong academic interest in medical microbiology, combined with experience in scientific research, clinical pharmacology and medical education. 

Presentation: Increased ceftriaxone exposure in hospitalised patients with decompensated cirrhosis compared to patients without cirrhosis revealed by population pharmacokinetic modelling (TACTILE study) 

Ceftriaxone is widely used in patients with decompensated cirrhosis. Cirrhosis-related pathophysiological changes may alter drug pharmacokinetics, resulting in unpredictable drug behaviour. This study investigated whether ceftriaxone exposure differs between patients with and without cirrhosis.

This multicentre observational study included patients with decompensated cirrhosis receiving intravenous ceftriaxone (2 g/day). Unbound plasma concentrations were compared with predictions from a published pharmacokinetic model developed in non-cirrhosis patients. Predictive performance was assessed using bias and precision. If bias and/or imprecision (≥25%) were observed, the model was refitted to characterise pharmacokinetic differences.

The analysis included 75 measurements from 19 patients (median age 62 years [range 30–77], eGFR 84 mL/min/1·73 m2 [range 22–139], Child–Pugh B [n=7], C [n=12]). Measured unbound concentrations were significantly underestimated by the pharmacokinetic model, with a bias of –25% (95% CI –38 to –11) and imprecision of 79% (95% CI 68–89). After refitting, renal function-adjusted clearance of unbound ceftriaxone was 4·2 L/h (95% CI 3·5–5·0) in cirrhosis versus 7·2 L/h (95% CI 6·3–8·2) in non-cirrhosis patients.

The TACTILE study showed increased unbound ceftriaxone exposure in cirrhosis, challenging the assumption that renally cleared drugs are unaffected by advanced liver disease and highlighting the need for cirrhosis-specific dosing.