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Three tetracycline analogues, tetracycline (TC), chlortetracycline (CTC) and oxytetracycline (OTC) have been used extensively in man and are well established as effective antimicrobial agents. Recently a fourth analogue, demethylchlortetracycline (DMCT) was described (1) and is being introduced for clinical use.' The structural formulas of these four tetracyclines are shown in Figure 1. Some of the important properties of the new analogue are: its resistance to heat, stability in acid and alkaline solution (1), good absorption with well-sustained blood levels (2-4) and antibacterial activity comparable to the best of the previously available analogues (1-5) and, in many instances, superior to them (5). The half-life of DMCTin serum following an oral dose was found to be 44 per cent longer than that of TC; this was shown to be related to the slower rate of renal excretion of the former (2). Thus, DMCTwas shown to produce much higher and better sustained levels of antibacterial activity in the serum than either TC (2, 3), CTC (3, 4) or OTC (4). The antibacterial spectra of the first three tetracyclines have been found to be identical, although some differences in their relative activity against certain organisms have been noted (5-12); the same is true for DMCT(5). An appreciation of the differences among the tetracyclines with respect to activity, physical properties, stability, solubility, plasma protein binding and absorption, distribution and excretion in sivo and toxicity should help to determine which, if any, may be

DISTRIBUTION AND EXCRETION OF FOUR TETRACYCLINE ANALOGUES IN NORMAL YOUNG MEN *