Comparative Pharmacokinetics of Dirithromycin and Erythromycin in Normal Volunteers With Special Regard to Accumulation in Polymorphonuclear Leukocytes and in Saliva

Eur J Clin Pharmacol. 1997;53(2):127-33. doi: 10.1007/s002280050350.

Abstract

Objective: In a randomized cross-over study, we assessed pharmacokinetics and intracellular concentrations in polymorphonuclear leukocytes (PMN) and saliva of erythromycin and erythromycylamine, the active metabolite of dirithromycin.

Methods: Ten healthy volunteers received 1 g erythromycin b.i.d. or 500 mg dirithromycin qd for 5 days (wash out period, 35 days). Concentrations of erythromycin and erythromycylamine were measured in serum, urine, saliva, and granulocytes by bioassay and high-performance liquid chromatography (HPLC) on days 1, 3, and 5 of each study period, respectively.

Results: While maximal serum concentrations (Cmax) and the area under the data (AUDtot) of erythromycin were significantly higher (Cmax 1.44 mg.l-1, AUDtot 5.66 mg.h.l-1) than those of erythromycylamine (Cmax 0.29 mg.l-1, AUDtot 1.96 mg.h.l-1), erythromycylamine had a significantly higher mean residence time (21 h) than erythromycin (5.5 h). Erythromycylamine accumulated significantly more in PMN than erythromycin; the accumulation factor of erythromycylamine was 100 with a maximal intracellular concentration of 13.4 mg.l-1, whereas the maximal accumulation factor of erythromycin was 4 with a maximal intracellular concentration of 6.1 mg.l-1. There were no significant differences in maximal saliva concentrations (erythromycin 0.35 mg.l-1, erythromycylamine 0.31 mg.l-1).

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / urine
  • Area Under Curve
  • Chromatography, High Pressure Liquid
  • Cross-Over Studies
  • Erythromycin / analogs & derivatives
  • Erythromycin / blood
  • Erythromycin / pharmacokinetics*
  • Erythromycin / urine
  • Female
  • Half-Life
  • Humans
  • Macrolides
  • Male
  • Neutrophils / chemistry*
  • Saliva / chemistry*

Substances

  • Anti-Bacterial Agents
  • Macrolides
  • dirithromycin
  • Erythromycin