Abstract
The pharmacokinetic profiles of single and repeated oral doses of telithromycin 800 mg/day were compared in patients with hepatic impairment and healthy subjects in two open-label, non-randomized, parallel-group, multicentre studies. The maximal plasma concentrations (
C
max) and the area under the plasma concentration–time (AUC) curves for telithromycin were similar in hepatically impaired patients and healthy subjects in the single- and repeated-dose studies. The extent of formation of RU 76363, the major circulating metabolite of telithromycin, was decreased following single and repeated doses in patients with hepatic impairment compared with healthy subjects. In the single-dose study, the
C
max of RU 76363 was 2-fold lower (
P<0.01) and the initial elimination half-life (
t
1/2
λ1
) was 44% higher (
P<0.01). The
C
max and AUC from 0 to 24 h post-dose were approximately 50% lower on Day 1 (
P⩽0.01) and Day 7 (
P⩽0.001) in the repeated-dose study. The terminal elimination half-life (
t
1/2
λz
) of telithromycin was 1.4-fold higher (
P<0.001) in the hepatically impaired patients compared with the healthy subjects in the single-dose study. However,
t
1/2
λ1
and
t
1/2
λz
were similar after repeated doses in both populations, suggesting that the decrease in formation of RU 76363 is compensated by an increase in clearance via other pathways. Telithromycin 800 mg was well tolerated in both populations. In conclusion, a once-daily dose of telithromycin is well tolerated in patients with hepatic impairment. Exposure to telithromycin was comparable in patients with hepatic impairment and healthy subjects and thus, no dosage adjustment is required in this patient group providing renal function is not severely impaired.