THE ENHANCEMENT OF SERUM PENICILLIN LEVELS IN MAN BY BENEMID|Sr*

The History and Future of Probenecid

“…The need for higher serum levels of antibiotics during this nascent era of antibiotic use and production was described by Boger et al [11] as ''when the daily doses of penicillin are large…measured in the millions of units… the economic aspects of this treatment become very important''. Before the introduction of probenecid, the other agents that were used to increase serum penicillin levels several fold by decreasing the antibiotic excretion in the urine [11], but either required prohibitively high doses (12-16 g of PAH continuous intravenous administration or up to 24 g carinamide oral administration) or had significant adverse effects (particularly nausea and vomiting) [54].…”

“…1). These had been proven to increase serum levels of penicillin and para-aminosalicylic acid (PAS), but their clinical application was limited due to undesirable side effects, or the need to be administered via constant intravenous drip or at extremely high oral doses [11,54]. A lower dose of probenecid was found to be as effective as carinamide and was used as adjunct therapy with penicillin.…”

A survey of problems in the antibiotic treatment of gonorrhoea. With special reference to South-East Asia.

“…Suitable after-peak levels can be maintained by multiple doses of the antibiotic (Table XXIII; Also both peak and subsequent levels of injectable* and orally administeredt penicillin preparations may *Beyer, Flippin, Verwey, and Woodward, 1944;Meads, Knight' and Izlar, 1951;Hilton, 1959;Robinson, 1964;Schmidt and Roholt' 1965;Evans, 1966;Gibaldi and Schwartz, 1968 tWhite, Couch Procaine penicillin TABLE XIX Repeated serum levels (u./ml.) after 2-4 m.u.…”

“…This may be given either in 0O5-g. doses 6-hrly or in 1-g. doses twice daily. When the latter dosage has been used a twofold enhancement of the penicillin level has been claimed, and when 3 g. have been given (1 g. 8-hrly) the increase has been five-fold or more (Meads, Knight, and Izlar, 1951).…”

Recent developments in the treatment of gonorrhoea.

“…Results obtained with 1-2 mega units procaine penicillin plus probenecid Use of the kidney-blocking agent probenecid (Meads, Knight, and Izlar, 1951) enhances the peak serum levels and duration of injectable and orally-administered penicillins, and excellent cure rates have been obtained in areas of high prevalence of resistant strains of gonococci (Jensen, Kvorning, and N0rredam, 1963;Schmidt and Roholt, 1965) by the use of injections of 5 mega units crystalline penicillin G plus one dose of 1 g. probenecid given 30 minutes before injection (Lomholt and Berg, 1966); the same dose of this penicillin preparation without probenecid would have produced unacceptable results. Holmes and others (1967), in the Far East, were able to reduce the failure rate with single injections of 2-4 mega units procaine penicillin from nearly 30 per cent.…”