Treatment of Gonorrhoea with Penbritin*

Although Sheehan (1958) had synthesized the penicillin nucleus 6-aminopenicillanic acid in 1958, it was not until 1959 that workers at the Beecham Research Laboratories (Batchelor, Chain, and Rolinson, 1961; Rolinson, Batchelor, Butterworth, Cameron-Wood, Cole, Eustace, Hart, Richards, and Chain, 1960) discovered a method of producing this compound on a large scale and made possible for the first time the synthesis of innumerable penicillin compounds. The first compound to stem from this research was phenethicillin (Broxil) an acid-stable preparation and hence suitable for oral administration. This preparation gives blood levels some two to three times higher than those obtained with penicillin V and as high or higher than those obtained with intramuscular injections of penicillin G. Unfortunately, however, this compound is eight times less effective in vitro against the gonococcus than is penicillin G., and various clinical trials gave disappointing results, the failure rate being as high or higher than with the earlier oral preparation penicillin V. Broxil was followed a year later by Methicillin (or Celbenin), an acid-labile penicillin which required to be given by intramuscular injection. We know of no published reports of its use in gonorrhoea, but a small personal trial in penicillin-resistant gonorrhoea showed that even multiple injections were completely ineffective. The outstanding property of Celbenin is its total resistance to penicillinase and its activity against bacteria other than staphylococci is low. Broxil and Celbenin were followed in 1961 by Penbritin 6 (D (-) a aminophenylacetamido) penicillanic acid (Ampicillin). Like Broxil, Penbritin is acid-stable and can thus be given orally. After a single dose of 1 g. the blood level rises comparatively slowly to reach a peak of between 6 and 7 t±g./ml. 2 hours after administration, significant concentrations being still present after 6 hours (Figs 1 and 2). Like other penicillins Penbritin is bactericidal and has a wide range of activity against both Grampositive and Gram-negative organisms. Hours