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.
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).
Uzzan
B
B
Laboratoire de Pharmacologie Clinique et Expérimentale, UFR Santé Paris-Nord, Bobigny, France.
Nicolas
P
P
Perret
G
G
Vassy
R
R
Tod
M
M
Petitjean
O
O
D000328:Adult; D001682:Biological Availability; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004311:Double-Blind Method; D006062:Gonadotropins / Q000097:blood; D006728:Hormones / Q000097:blood*; D006801:Humans; D015570:Josamycin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects*; D008111:Liver Function Tests; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D011863:Radioimmunoassay; D013963:Thyroid Hormones / Q000097:blood / Q000378:metabolism; D014217:Troleandomycin / Q000494:pharmacology*
D006062:Gonadotropins; D006728:Hormones; D013963:Thyroid Hormones; D003577:Cytochrome P-450 Enzyme System; D014217:Troleandomycin; D015570:Josamycin