Table 3.
Itraconazole and ketoconazole studies included in the systematic review.
| Author, year | Study population (N) | Study type | Dose, Duration | Sampling times | Saliva sampling + stimulation |
Analytical method | Saliva Cmax (mg/L), AUC0-24 (mg.h/L) |
Plasma Cmax (mg/L), AUC0-24 (mg.h/L) |
S/P ratio, correlation | S/P ratio based on | Support saliva TDM (Y, I, N, N/A) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Itraconazole | |||||||||||
| Reynes et al. (1997) | HIV patients (+/− AIDS), N = 23 |
Prospective cohort PK study | Suspension, 100mg po bd, 14 days | 0, 2, 4, 8 h on day 1 & day 14 | syringe | Reverse-phase HPLC | without AIDS: 1.64 ± 2.05k, _ with AIDS: 4.07 ± 3.91 _ (no active metabolite detected in saliva) |
without AIDS: 0.95 ± 0.38, AUC0–10: 7.78 ± 3.14 with AIDS: 0.70 ± 0.39, AUC0–10: 6.25 ± 3.86 |
Variable | C at multiple time-points (day 14) | N |
| Cross et al. (2000) | Patients, N = 40 |
Randomized, formulation comparison study | Suspension, 100mg po bd, 15 days |
random, day 15 (median t = 4 h) | tubes | Reverse-phase HPLC | C random times, 0.12 (IQR 0–0.53) |
C random times, 0.74 mg/L (IQR 0.46–1.18) |
0.115 (0-3.71)l | C at multiple time-points, day 15 | N |
| Capsules, 100mg po bd, 15 days |
random, day 15 (median t = 3 h) | tubes | Reverse-phase HPLC | not detectedm | C random times, 0.61 (IQR 0.37–0.93) |
0 | C at multiple time-points, day 15 | N | |||
| Ketoconazole | |||||||||||
| Force and Nahata (1995) | HV, N = 8 |
Randomized cross over (with fluconazole) study | 400mg po, single (tablet) |
0, 1, 2, 3, 6, 12, and 24 h | tubes | HPLC | 0.119 ± 0.050 _ |
7.64 ± 3.87 _ |
0.011 | Cmax | N |
knote high variability (high SD), explains no statistically significant differences between patients with vs. without AIDS; lcalculated from data presented in the study;
mtwo patients had aberrantly high saliva concentrations, which were considered due to sampling or analytical error; C, concentration.