Table 2

Noncompartmental PK parameter estimates for fusidic acida

StudyCohortNDose (mg)Dosing intervalDose no.bGeometric mean (% CV)c of PK parameter
Cmax (mg/liter)Tmax (h)t1/2 (h)AUC0–12 h (mg · h/liter)AUCDosed (mg · h/liter)CLT/F (liters/h)Vss/F (liters)
10316550Single131.2 (32)2.0 (2.0, 3.0)20.4 (25)222 (42)377 (59)1.40 (59)22.5 (40)
655012 h130.7 (35)2.0 (1.5, 2.0)193 (41)
655012 h231.1 (45)7.0 (1.0, 8.0)239 (53)
655012 h11105 (40)3.0 (1.5, 4.0)13.5 (25)886 (50)886 (50)0.596 (65)12.8 (60)
261,100Single171.5 (15)3.5 (1.0, 4.0)17.7 (9)561 (15)1,072 (23)0.984 (20)15.5 (8)
61,10012 h182.7 (18)1.5 (1.5, 3.0)536 (7)
61,10012 h2102 (48)4.0 (3.0, 11.5)737 (20)
61,10012 h11276 (19)4.0 (4.0, 8.0)16.7 (31)2,483 (16)2,483 (16)0.425 (22)14.2 (16)
361,650Single199.4 (25)3.0 (2.0, 4.0)15.1 (15)808 (28)1,662 (39)0.952 (49)17.8 (18)
51,65012 h190.8 (20)4.0 (2.0, 8.0)682 (12)
51,65012 h2105 (7)8.0 (2.0, 11.5)979 (8)
51,65012 h11316 (7)4.0 (1.5, 4.0)26.1 (61)3,304 (4)3,304 (4)0.479 (4)24.6 (42)
462,200Single1126 (22)6.0 (3.0, 8.0)16.3 (26)981 (25)2,493 (39)0.846 (47)17.1 (32)
61,10012 h164.5 (22)e2.5 (1.5, 4.0)507 (27)e
61,10012 h282.7 (31)e7.0 (2.0, 11.5)767 (31)e
650012 h15141 (26)e4.0 (3.0, 6.0)18.0 (40)1,370 (25)e1,370 (25)e0.385 (21)10.2 (20)
561,65012 h191.8 (21)2.5 (2.0, 6.0)819 (16)
61,65012 h2157 (11)3.5 (1.5, 8.0)1,537 (11)
682512 h15259 (12)e3.5 (3.0, 4.0)29.3 (35)2,551 (13)e2,551 (13)e0.310 (12)14.3 (29)
102-A28500SingleFasted27.4 (23)3.0 (1.0, 4.0)11.8 (22)182 (26)314 (31)1.53 (32)21.0 (27)
14f500SingleFasted28.4 (20)2.5 (1.0, 4.0)11.8 (22)197 (20)342 (25)1.40 (24)19.4 (24)
14500SingleFed21.2 (24)3.5 (1.5, 6.0)11.5 (26)152 (25)281 (35)1.71 (31)24.5 (30)
102-B175008 h13146 (25)3.0 (0.5, 6.0)18.0 (29)1,030 (26)g1,030 (26)0.466 (25)13.1 (23)
  • a N, number of healthy subjects; Dose no., number of doses administered; Single, single dose; Cmax, maximum observed concentration; Tmax, time of Cmax postdose; t1/2, apparent half-life during the terminal phase; AUC0-12h, area under the curve from time zero to 12 h; AUCDose, area under the curve from time zero to infinity for a single dose or area under the curve during one dosing interval after the last dose for a multiple-dose regimen; F, (unknown) extent of bioavailability after oral dosing; CLT/F, apparent total clearance; Vss/F, apparent volume of distribution at steady state.

  • b Dose numbers 1, 11, 13, and 15 refer to morning doses; dose number 2 refers to evening doses.

  • c Median (minimum, maximum) is reported for Tmax.

  • d The comparison of AUCDose after single and multiple doses assumes that steady state was achieved after multiple dosing. If steady state had not been achieved, AUCDose would be expected to be even higher and CL/F lower after multiple doses compared to the estimates reported.

  • e Please note that multiple doses were lower than single dose for cohorts 4 and 5. For cohorts 1, 2, and 3, single and multiple doses administered were the same.

  • f Data for the 14 subjects who received sodium fusidate in the fasted and fed state within study 102-A are reported in this row to support the conclusions for the effect of food on the rate and extent of bioavailability. These 14 subjects are part of the 28 subjects receiving sodium fusidate in the fasted state.

  • g Area under the curve from 0 to 8 h.