Effects of troleandomycin and josamycin on thyroid hormone and steroid serum levels, liver function tests and microsomal monooxygenases in healthy volunteers: a double blind placebo-controlled study

Abstract

Serum TSH levels are moderately but significantly (P ANOVA: 0.05) decreased by troleandomycin (T; 1 g bid over a 10-day period) compared with josamycin (J) (same doses) and placebo (P) in healthy volunteers. T also significantly increases serum estradiol concentration (P ANOVA: 0.03). This effect may be related to a T-induced inhibition of some P450 monooxygenase isoenzymes and more specifically P 450 NF, determined in our study by a decrease in urinary excretion of 6-beta-hydroxy-cortisol. Troleandomycin and josamycin both show poor upper GI tolerance. Liver enzymes (SGOT, SGPT, alkaline phosphatase and gGT) are significantly altered by T compared with J and P (P ANOVA: 0.007, 0.001, 0.09 and 0.04 respectively). After J, liver function tests are very close to control values (placebo). Liver enzymes are significantly more altered by T than by J (P 0.004, 0.001 and 0.06 for SGOT, SGPT and gGT respectively). Using 6 volunteers in a latin-square designed study, some established effects of oral macrolides were confirmed (poor upper GI tolerance; liver toxicity of T). Some other effects of T were also elicited, which were either unknown (decrease in serum TSH) or expected but which had not previously been assessed in man (increase in serum estradiol; decreased urinary excretion of 6-beta-hydroxy-cortisol).