Table 2.
Ciclosporin pharmacokinetics without and with fluconazole (400 mg day−1) in 12 healthy volunteers
| Parameter | Ciclosporin | Ciclosporin + fluconazole | P |
|---|---|---|---|
| All | |||
| Dose (mg) | 125 (100–200) | 55 (40–100) | <.01 |
| C0 (μg L−1) | 87 (77–98) | 76 (70–82) | .14 |
| Cmax (μg L−1) | 900 (807–1004) | 580 (513–657) | <.01 |
| AUC(0–12) (h μg L−1)a | 3,009 (2,755‐3,287) | 2,426 (2,219‐2,652) | .02 |
| Steady‐state b | |||
| Dose (mg) | 125 (100–200) | 67.5 (40–100) | .01 |
| C0 (μg L−1) | 81.7 (69.2–96.4) | 78.8 (73.6–84.3) | .69 |
| Cmax (μg L−1) | 852 (742–979) | 584 (487–700) | <.01 |
| AUC(0–12) (h μg L−1)a | 2,976 (2,681‐3,304) | 2,539 (2,254‐2,860) | .12 |
| AUC(0–12) (h μg L−1 per mg ciclosporin) | 23.2 (19.8–27.1) | 40.7 (32.2–51.3) | <.01 |
| tmax (h) | 1.5 (1.0–2.0) | 2.0 (1.0–3.0) | .25 |
| CL/F (L h−1) | 43.0 (36.9–50.3) | 24.6 (19.5–31.0) | <.01 |
| V/F (L) | 305 (257–363) | 184 (151–226) | <.01 |
| t1/2 (h) | 4.9 (4.2–5.8) | 5.2 (4.8–5.6) | .42 |
All values are reported as geometric mean and 90% confidence interval, except dose and tmax, which are reported as median and range.
AUC, area under the curve; C0, predose concentration; CL/F, apparent clearance after oral administration; Cmax, maximum concentration; t1/2, half‐life; tmax, time of maximum concentration; V/F, apparent terminal volume of distribution after oral administration.
a
The results for AUC0–10 were essentially the same as reported for AUC0–12.
b
n = 8, after exclusion of participants requiring ciclosporin dose adjustments within 2 days before a day when ciclosporin pharmacokinetics was determined.