Table 1 Overview of pharmacokinetic parameters and dosing regimens of antifungals for intra-abdominal candidiasis
| Â | First-line agents | Second-line agents | ||||
|---|---|---|---|---|---|---|
Fluconazole | Caspofungin | Anidulafungin | Micafungin | Liposomal amphotericin B | Voriconazole | |
Healthy volunteer | ||||||
Recommended dosing regimen | LD 800 mg (12 mg/kg) MD 400 mg (6 mg/kg) | LD 70 mg MD 50 mg (70 if BW > 80 kg) | LD 200 mg MD 100 mg | 100 mg | 3–5 mg/kg | LD 6 mg/kg q12h MD 4 mg/kg q12h |
Cmax (mg/L) | 9 | 9.5–12 | 7–8 | 8–18 | 58–90 | 3.1–4.7 |
AUC (mg/h/L) | 90–100 | 98 | 110 | 66 | 713 | 13–33 |
Vd (L/kg) | 0.7–0.8 | 0.15–2 | 0.6 | 0.2 | 0.2–1.6 | 4.6 |
Protein binding (%) | 12 | 92.4–96.5 | 99.0 | 99.9 | 95–99 | 58 |
Half-life (h) | 25–40 | 9–11 | 40–50 | 11–20 | 13–34 | 6 |
CL (mL/min) | 15–46 | 10–12 | 1 | 12.8–14 | 11 | 250 |
Critically ill patient | ||||||
Proposed dosing regimen | LD 12 mg/kg MD 6 mg/kg | LD 100–140 mg MD 50–70 mg | LD 200 mg MD 100 mg | LD 150 mg MD 150 mg | 5 mg/kg | LD 6 mg/kg q12h MD 4 mg/kg q12h |
Vd (L/kg) | 1.2–1.4 | 0.1 | 0.5 | 3.45 | 0.42 | 4.3 |
Half-life (h) | 30–75 | 18.4 | 31.2 | 14.8 | 13 | 13–21 |
CL (mL/min) | 13–36 | 13 | 17.1 | 12.2 | 0.36–1.4 | 61–99 |
Renal impairment | Decreased dose by 50% when renal CL < 50 mL/min | No dose adjustment | No dose adjustment | Switch to oral formulation when creatinine CL  < 50 ml/min | ||
CRRT | LD 12 mg/kg MD 6 mg/kg Consider increasing the dose if ultrafiltration rate > 2L/h Or 300–400 mg q12 | No dose adjustment | No dose adjustment | |||
Hepatic impairment | Limited date, no specific recommendations | Child Pugh 7–9, decrease MD to 35 mg q24h | No dose adjustment | No dose adjustment | Limited data, no specific recommendations | Reduced maintenance dose of 50% |
Hypoalbuminemia | No data | MD 50–70 mg according to the MIC | Reduced AUC but not defined dose | Reduced AUC but not defined dose | No data | Considered unbound concentration to be 50% higher than the total measured concentration |
Obesity | Avoid fixed–dose, use weight-based dosing (TBW) LD 12 mg/kg MD 6–12 mg/kg | Increased the LD and MD by at least 25 to 50% when body weight > 80–120 kg LD 2 mg/kg MD 1.25 mg/kg | Increased the LD and MD by 25% in patients > 140 kg | Increased the MD from 100 to 300 mg according to the MIC when body weight > 125 kg | Avoid fixed–dose, use weight-based dosing (TBW) 5 mg/kg | Avoid fixed–dose, use weight-based dosing (ABW) (based on non-ICU patients) |
ECMO | No data in adult patients | Increased the MD to 70 mg | No dose adjustment | Increased the MD to 150 mg | Only case reports suggesting increasing of the MD and/or change for extended infusion or switch for amphotericin B deoxycholate | Circuit loss reported but no specific recommendations |
Therapeutic drug monitoring | ||||||
PK/PD target | fAUC0-24/MIC  ≥ 100 | AUC0-24/MIC > 250 (C. tropicalis/krusei) 450 (C.glabrata)–865 (C.albicans)–1185 (C.parapsilosis) | AUC24/MIC > 2000 (C.parapsilosis)–3000 (C.glabrata)–9000 (C.albicans) | AUC24/MIC > 3000 (C.glabrata/parapsilosis)–10,000 (C.albicans) | Not defined | fAUC24/MIC > 25–100 |
Therapeutic range (AUC) mg/h/L |  > 400 |  > 100 | 110 |  > 130 | Not defined | Not defined |
Therapeutic range (Cmin) mg/L | 10–15 | 1–10 | 1–10 | 1–10 | Not correlated with efficacy | 2–6 (MIC of 1 mg/L) |