Entry of four tetracyclines into saliva and tears

Abstract

Although meningococci are susceptible to the tetracyclines by testing in vitro, oxytetracycline (OC) and doxycycline (DC) have failed to eliminate carriage, whereas minocycline (MC) has been effective. Because these congeners differ in lipophilicity, they and tetracycline (TC) were studied in volunteers by assay of serum, saliva, and tears obtained after 5 days of treatment. OC and TC were undetectable or attained concentrations subinhibitory for meningococci in saliva and tears. The concentrations of MC in saliva and tears were equal to or greater than the average minimal inhibitory concentration as long as 12 h post-dose. Near inhibitory concentrations resulted with DC at 100 mg/day; yet, doubling the dose to 100 mg/12 h did not yield concentrations that exceeded the average minimal inhibitory concentration for meningococci. The previous reports of failure or meager entry of DC and MC into saliva probably reflected extraction of these drugs in the paraffin chewed by subjects to stimulate salivary flow. The efficiency of entry of the tetracyclines into the secretions of the noninflamed upper respiratory tract correlates with lipophilicity at physiological pH, enabling prediction of meningococcal chemoprophylactic efficacy.