Table 5.
Pharmacokinetics of echinocandins in LD patients
| Study | Study characteristics | PK in LD patients |
|---|---|---|
| Caspofungin | ||
| Mistry et al112 | Single-dose, open-label study of 70 mg per day for 14 days | • Increased AUC, Cmin and β-phase half-life compared with the healthy control subjects • Dose reduction to 35 mg daily following 70 mg is recommended for moderate and severe LD patients |
| Spriet et al169 | Case study of ICU patient with Child-Pugh score B9 (70 mg on day 1 followed by maintenance dose of 50 mg/day) | • AUC is comparable to that of healthy subjects (no higher systemic exposure is observed) • Dose reduction is not recommended |
| Spriet et al169 | Case study of ICU patient with Child A liver cirrhosis and transjugular intrahepatic portosystemic shunt | • Similar exposure and PK parameters compared to the healthy volunteers • Dose reduction not recommended |
| Micafungin | ||
| Undre et al124 | Single dose, open-label with severe hepatic dysfunction (Child-Pugh score 10–12) | • Low Cmax, low AUC in severe LD patients compared to healthy subjects (not clinically relevant) |
| Hebert et al125 | Phase 1, parallel-group, open-label PK study of single dose IV micafungin in eight moderate LD patients (Child-Pugh score 7–9) | • Lower AUC, Cmax in moderate LD patients compared to healthy volunteers, but no difference in clearance and volume of distribution or half-life • No change in unbound plasma concentration compared to that of healthy controls. • Given that low AUC is attributed to weight difference, dose reduction is not recommended |
| Anidulafungin | ||
| Dowell et al133 | Phase 1, open-label, single-dose prospective study in adult patients at two clinical sites | PK parameters of mild and moderate LD patients were comparable to healthy controls. Decreases in AUC and Cmax in severe LD patients were observed compared to healthy subjects (not clinically relevant, probably due to increase in VD due to ascites and edema). However, half-life in LD patients was comparable to healthy subjects |
Abbreviations: AUC, area under the curve; ICU, intensive care unit; LD, liver disease; PK, pharmacokinetics; VD, volume of distribution; β-phase half-life, elimination half-life.