Tonsillar penetration of erythromycin and its 2'-acetyl ester in patients with chronic tonsillitis

Abstract

Concentrations of erythromycin and 2'-acetyl erythromycin were analysed in serum or plasma and tonsil tissue after repeated dosage of erythromycin acistrate (EA), a new erythromycin prodrug, in two separate studies in 61 young patients. The reference preparations were: (1) enterocoated tablets of erythromycin base (EB enterotablets, (2) erythromycin base as enterocoated pellets (EB enterocapsules) and (3) erythromycin stearate (ES). All drugs were given 500 mg tid for three days before scheduled tonsillectomy. Tonsils were removed about 3 h after intake of the last dose. Blood samples were collected at 0, 2 and 6 h and at the time of tonsillectomy. At all time points EA produced several-fold higher total drug (erythromycin + 2'-acetyl erythromycin) concentrations in serum or plasma than any of the reference preparations. Similarly, after EA the mean total antibiotic levels in tonsil tissue exceeded the erythromycin levels after the reference preparations by at least a factor of 3. Tonsil/serum or plasma ratios of the total antibiotic were quite similar with all preparations (means 38-50%). Peak erythromycin levels in circulation did not differ significantly from each other in spite of two nonabsorbers after EB enterotablets. The same was true of tonsil tissue. There were, however, 15 tonsils with undetectable erythromycin: 4/25 (16%) with EA, 5/12 (42%) with EB enterotablets, 2/12 (17%) with EB enterocapsules and 4/12 (33%) with ES. The degree of hydrolysis of 2'-acetyl erythromycin to erythromycin was 23-43% higher in tonsil tissue than in circulation.

Amphiphilic Erythromycin-Lipoamino Acid Ion Pairs: Characterization and In Vitro Microbiological Evaluation

“…The experimental solubility data suggest that LAA ion pairs of ERY possess an amphiphilic character, which can become helpful both for the formulation of controlled delivery carriers of this antibiotic, and for modifying the absorption profile of the drug after systemic administration. For instance, ERY salts and prodrugs have been shown to have different oral absorption levels and times than the free antibiotic (6,26,27), as well as to give different local bioavailability than ERY in specific sites (28)(29)(30).…”

Issues in Pharmacokinetics and Pharmacodynamics of Anti-Infective Agents: Distribution in Tissue

“…In particular, antibiotic failures have been attributed to impaired target site penetration in cases of soft tissue infections (134), osteomyelitis and orthopedic surgery (45,98,127), peridontitis and odontogenic infections (1), endocarditis (94), septic embolism (14,142), foreign body-and catheter-related infections (142), gastric ulcer (67), hematomas (142), epidermal infections (101), abscesses (142), granuloma-inducing infections and tuberculosis (51,186), prostatitis (46), eye infections (21), ear infections (69), tonsillitis (136), sinusitis (50), liver infections (139), urinary tract infections (116,142), pelvic inflammatory disease (122), solid malignancies (79,129), respiratory tract infections (126,131), heart-lung bypass surgery (22), and septic shock (80).…”

Tissue kinetics of telithromycin, the first ketolide antibacterial

“…In addition, the tonsillar penetration of telithromycin compares favourably to that of the macrolides erythromycin and dirithromycin. [62][63][64] Although azithromycin and clarithromycin achieve higher tonsillar concentrations than telithromycin, their concentrations do not exceed their MIC values for any macrolide-resistant strains of GABHS at any point during the dosing period. 65,66 Telithromycin concentrations however peaked at levels in excess of the MIC 90 values for macrolide-resistant [mef(A)or erm(TR)-positive] GABHS.…”