Nevertheless, the authors neither reported the antacid dosage and the dosing interval nor indicated whether the antacid intake was concomitant or delayed with ...
Letters to the Editor Antacids and Ciprofloxacin Pharmacokinetics We wish to congratulate Dr. Golper and collaborators on the excellent research on ciprofloxacin in continuous ambulatory peritoneal dialysis (1). Nevertheless, the authors neither reported the antacid dosage and the dosing interval nor indicated whether the antacid intake was concomitant or delayed with respect to ciprofloxacin administration. This information could have been interesting, since the interaction between quinolones and antacids to form chelated complexes has been well documented (H. C. Neu, Quinolone Bull. 2:1, 1985; P. M. Sah, Quinolone Bull. 2:12, 1986); in addition, some controversial data concerning the extent of this interaction have been published (2, 3). In fact, the influence on quinolone kinetics exerted by antacids seems to depend especially on their dosage and dosing schedule. For this reason, a 2-h interval between the concomitant administration of cation-containing antacids in therapeutic doses and quinolones has been advised (4).
3. Maesen, F. P. V., B. I. Davies, W. H. Geraedts, and C. A. Sumajow. 1987. Ofloxacin and antacids. J. Antimicrob. Chemother. 19:848-849. 4. Spino, M. 1987.The quinolones: an important new group of drugs for the elderly. Can. Pharm. J. 120:242-252. Walter Bianchi Franco Maggiolo Alberto Imbasciati Heinrich K. P. Ohnmeiss Medical Department Bayer Italia S.p.A. 20156 Milan, Italy
Author's Reply We gratefully accept and concur with the comments of Bianchi and associates. Our patients received from 1 to 3 g of aluminum hydroxide 1 h prior to the morning dose, again at lunch, and 2 h after the evening dose of ciprofloxacin. In addition to the role of antacids, uremia and continuous ambulatory peritoneal dialysis may have effects on the oral absorption of ciprofloxacin.
LITERATURE CITED 1. Golper, T. A., A. I. Hartstein, V. H. Morthland, and J. M. Christensen. 1987. Effects of antacids and dialysate dwell times on multiple-dose pharmacokinetics of oral ciprofloxacin in patients on continuous ambulatory peritoneal dialysis. Antimicrob. Agents Chemother. 31:1787-1790. 2. Hoffken, G., K. Borner, P. D. Glatzel, P. Koeppe, and H. Lode. 1985. Reduced enteral absorption of ciprofloxacin in the presence of antacids. Eur. J. Clin. Microbiol. 4:345.
Thomas A. Golper Division of Nephrology Oregon Health Sciences
University Portland, Oregon 97201
Structure of Adenylylated Streptomycin Synthesized Enzymatically by Bacillus subtilis A chromosomal streptomycin adenylyltransferase was detected in derivatives of Bacillus subtilis Marburgl68. The properties of the enzyme purified from one of the derivatives, BD224 (2), were investigated in our previous paper (3). To define the aminoglycoside adenylyltransferase (AAD), we determined the structure of the adenylylated streptomycin before studying the role of the AAD-producing gene in producing streptomycin resistance. The relationship to resistance is important because high levels of the enzyme were detected in a streptomycin-susceptible B. subtilis derivative. Streptomycin (20 mg) was inactivated by the crude extract of strain BD224 by a method described before (3). The inactivated streptomycin was purified by the method of Suzuki et al. (7) using columns of carboxymethyl celluloseSephadex C25 (NH4+), Amberlite IRC50 (Na+), and Sephadex G10. One milligram of purified inactivated streptomycin was obtained. Mass spectra of streptomycin, AMP. 2Na, and inactivated streptomycin obtained by secondary ion mass spectrometry (M-80; Hitachi Ltd., Tokyo, Japan) were as follows: streptomycin (molecular weight, 581), m/z 582 [M + H]+ and 674 [M + glycerol + H]+; AMP. 2Na (molecular weight, 391), mlz 392 [M + H]+ and 414 [M + Na]+; and inactivated streptomycin, mlz 955 [M + Na]+. Therefore,
inactivated streptomycin (UV maximum, 260 nm) appears to be a monoadenylylated streptomycin sodium salt (molecular weight, 932). 'H nuclear magnetic resonance (NMR) (400 MHz, D20, pH 5.5) and 13C NMR (100 MHz, D20, pH 5.5) spectra of inactivated streptomycin and a mixture of streptomycin and AMP (molar ratio, 1/1; 3.4 ,umol) were determined with water as the internal standard (5 = 4.78, 25°C) and 3(trimethylsilyl)propionic acid-d4 sodium salt as the external standard (5 = 0, 25°C). The assignments of peaks in the 'H and 13C NMR spectra of streptomycin and AMP were based on data reported before (1, 4-6) (Table 1). It was found that both the position and the strength of the 3"-H signal (3.90 to 3.95 ppm), which overlapped one of the 6"-H signals of N-methyl-L-glucosamine in streptomycin, were not significantly changed in inactivated streptomycin. A new signal appeared at 4.01 ppm, which may represent the 6-H signal of inactivated streptomycin. The C-6 signal (74.4 ppm) in streptomycin underwent a low-field shift of 5.1 to 79.5 ppm in inactivated streptomycin. Furthermore, the C-1 signal (61.7 ppm) of streptomycin showed a low-field shift to 62.5 ppm in inactivated streptomycin. However, the signal for C-3" (72.5 ppm) remained unchanged. Thus, we concluded that the structure of streptomycin 949
