Pharmacokinetics of dirithromycin in patients with mild or moderate cirrhosis

The pharmacokinetics of dirithromycin were determined over a 72-h period fo llowing oral administration of a single 500-mg dose to 8 healthy volunteers and to 16 cirrhotic patients (8 patients with class A cirrhosis and 8 pati ents with class B cirrhosis according to Pugh's & Child's classification). Drug levels in plasma and urine were determined by microbiological assay. T he mean maximum concentrations of drug in serum obtained 3 to 4 h after adm inistration were 0.29 +/- 0.22 mg/liter in volunteers and 0.48 +/- 0.21 and 0.52 +/- 0.38 mg/liter in patients with class A and class B cirrhosis, res pectively. The elimination half-life (t(1/2 beta)) was 23.3 +/- 7.6 h in he althy subjects and 35.2 +/- 11.8 h and 39.5 +/- 11.0 h in patients,vith cla ss A and class B cirrhosis, respectively. The mean area under the concentra tion-time curve (AUC) and t(1/2 beta) were significantly higher in patients with class A and B cirrhosis than in healthy controls, while total and ren al clearances were markedly reduced (P < 0.01). The time to the maximum con centration of drug in serum and the volume of distribution values appeared to be similar in all groups, and the mean recovery in urine at 72 h ranged from 3.7 to 5.7%, without significant differences among groups. These resul ts demonstrate that some dirithromycin kinetic parameters are significantly different in cirrhotic patients in comparison to those in healthy voluntee rs. However, an increase in the t(1/2 beta) or AUC, which is also observed with other semisynthetic macrolides (e.g., azithromycin), does seem to be n ot clinically relevant if one takes into account both the high therapeutic indices of these antibiotics and the usually short duration of therapy. The refore, on the limited basis of single-dose administration, no modification s of dirithromycin dosage seem to be required even for patients with class B liver cirrhosis.