Maximum Itraconazole Plasma Concentration After Oral 200 mg Dose
Peak plasma concentrations of itraconazole reach approximately 0.16 mcg/mL (160 ng/mL) at 3-4 hours after a single oral 200 mg dose in healthy adults, though this can vary significantly based on formulation and fed/fasted state. 1, 2
Pharmacokinetic Parameters for Single Dose
The FDA label specifies that peak plasma concentrations are reached within 2.5 hours following administration of the oral solution, with the observed absolute bioavailability being approximately 55% under fed conditions and increasing by 30% when taken in fasting conditions. 1
Key Concentration Data:
- Single 100 mg oral dose: Peak plasma level of 0.16 mcg/mL at 3-4 hours post-administration 2
- Single 200 mg oral dose: By extrapolation, approximately 0.32 mcg/mL (320 ng/mL) would be expected, though non-linear pharmacokinetics may affect this 1, 2
- Formulation matters significantly: The oral solution provides greater exposure than capsule formulation at the same dose 1
Important Clinical Context
Steady-State vs. Single Dose Concentrations
Single-dose concentrations are substantially lower than steady-state levels. The FDA label indicates that steady-state Cmax values of approximately 2 mcg/mL (2000 ng/mL) are reached after 200 mg once daily for about 15 days, representing a 4- to 7-fold accumulation compared to single-dose values. 1
Factors Affecting Peak Concentration:
- Food effect: Capsule formulation should be given with a full meal to optimize absorption, while solution should be given 1 hour before or after meals (43% increase in bioavailability when fasted) 3
- Formulation differences: SUBA-itraconazole (super bioavailability formulation) achieves higher concentrations at lower doses 3
- Protein binding: 99.8% of itraconazole is bound to plasma proteins, with only 0.2% present as free drug 1
Therapeutic Implications
For clinical efficacy, single-dose concentrations are generally insufficient. Guidelines recommend:
- Prophylaxis: Trough concentrations >0.5 mcg/mL (500 ng/mL) 3, 4, 3
- Treatment of invasive infections: Trough concentrations between 1-2 mcg/mL (1000-2000 ng/mL) 3
- Upper safety limit: Concentrations >5 mcg/mL associated with increased mortality 3
Critical Caveat:
The terminal half-life after a single dose is approximately 24 hours, but this increases to 34-42 hours with repeated dosing due to saturable hepatic metabolism. 1 This means therapeutic monitoring should focus on steady-state trough levels (measured 2-4 hours after a dose at steady state), not single-dose peak concentrations. 5, 4