Antibiotic concentration in suction skin blister fluid and saliva after repeated dosage of erythromycin acistrate and erythromycin base

Abstract

The drug concentration in plasma, suction skin blister fluid (SBF), urine and saliva after repeated dosage of either erythromycin acistrate (EA) or enterocoated pellets of erythromycin base (EB) was studied in young healthy volunteers with a cross-over design in two separate studies. In Study I, the total drug concentration (erythromycin +2′-acetyl erythromycin) after EA (400 mg tid) was slightly higher than the erythromycin concentration after EB (500 mg tid). The concentration of erythromycin after EA was about half of that after EB. In SBF the total antibiotic concentration after EA and erythromycin concentration after EB were 49 and 46% of the corresponding plasma concentrations, respectively. The degree of hydrolysis of 2′-acetyl erythromycin was higher in SBF (44%) than in plasma (39%). An equal proportion (7·3−7·5%) of the dose was excreted in urine after administration of both drugs. The degree of hydrolysis of 2′-acetyl erythromycin in urine was 58%. In Study II, the plasma/saliva concentration ratio ranged from 0·11 to 0·17 after EA 400 mg tid, 0·12 to 0·20 after EA 500 mg tid and 0·17 to 0·22 after EB 500 mg tid. The degree of hydrolysis of 2′-acctyl erythromycin was considerably higher in saliva (61–78%) than in plasma (27–41%). In plasma, the percentage of hydrolysis of 2′-acetyl erythromycin was inversely correlated with the concentration of acid-α ₁ -glycoprotdn. The penetration of 2′-acetyl erythromycin and erythromycin into the extravascular space as evaluated from SBF and saliva levels was equal, and adequate concentrations of erythromycin were obtained for the treatment of bacterial infections. In vivo , the percentage of hydrolysis of 2′-acetyl erythromycin is obviously dependent on the protein binding of the prodrug.