Comparative pharmacokinetics of dirithromycin and erythromycin in normal volunteers with special regard to accumulation in polymorphonuclear leukocytes and in saliva.
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).
Geerdes-Fenge
H F
HF
Department of Pulmonary and Infectious Diseases, City Hospital Lungenklinik Heckeshorn, affil. Freie Universität Berlin, Germany.
Goetschi
B
B
Rau
M
M
Borner
K
K
Koeppe
P
P
Wettich
K
K
Lode
H
H
D000284:Administration, Oral; D000328:Adult; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004917:Erythromycin / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005260:Female; D006207:Half-Life; D006801:Humans; D018942:Macrolides; D008297:Male; D009504:Neutrophils / Q000737:chemistry*; D012463:Saliva / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D018942:Macrolides; C053853:dirithromycin; D004917:Erythromycin