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Sinus Tissue Pharmacokinetics After Oral Administration of Amoxicillin/Clavulanic Acid
Author(s) -
Borges Dinis Paulo,
Conceição Monteiro Maria,
Luz Martins Maria,
Silva Nuno,
Gomes Augusto
Publication year - 2000
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1097/00005537-200006000-00030
Subject(s) - clavulanic acid , amoxicillin , medicine , amoxicillin/clavulanic acid , sinusitis , pharmacokinetics , antibiotics , streptococcus pneumoniae , pharmacology , microbiology and biotechnology , surgery , biology
Objectives The in vitro synergy of the amoxicillin/clavulanic acid combination has not always translated in vivo into clinical superiority compared with amoxicillin alone. Specifically, conflicting reports have disputed the superiority of the combination in the treatment of both acute otitis media and acute sinusitis. One possible reason for this may have to do with inadequate target tissue pharmacokinetics. To explore this possibility in the sinuses, we undertook the present investigation. Study Design A randomized, open, single‐dose, sinus tissue pharmacokinetic study with oral amoxicillin/clavulanic acid. Methods Twenty‐three adult patients with chronic rhinosinusitis who had been selected for surgery were randomly allocated to receive a tablet of 875/125 mg amo‐icillin/clavulanate 2 to 4 hours before surgery began. During the operation tissue samples were collected at specific sinonasal sites for determination of both amo‐icillin and clavulanic acid concentration levels. Results Amoxicillin displayed adequate tissue levels throughout the sinuses, high enough to cover common susceptible pathogens. However, the presence of clavulanate was detected in only half of the sinonasal tissue samples. Conclusions The kinetics of oral clavulanic acid apparently fails to provide a widespread anti–β‐lactamase activity capable of enhancing the activity of amoxicillin in all parts of the sinuses. Despite this, amoxicillin/clavulanic acid maintains a central role in the treatment of acute rhinosinusitis, because amoxicillin is still the most effective oral β‐lactam against Streptococcus pneumoniae , a particularly virulent and increasingly resistant upper respiratory tract pathogen. Also, as our data show, a concomitant anti–β‐lactamase activity can be expected to occur, although in an unpredictable fashion.