Kohya Shiba

Suppressive effects of minocycline on the pituitary-thyroid axis in humans

Minocycline has been thought to induce “black thyroid”, a condition marked by discoloration due to brown deposits. However, its effect on thyroid function in humans is still obscure. We conducted a prospective study of thyroid hormone levels in 17 patients who were administered 200 mg minocycline daily for 10 days. We found that minocycline significantly reduced the serum total thyroxine level (8.43±0.61 to 7.09±0.45 μg/dl, mean ± SEM;P<0.01), and free thyroxine level (1.12±0.10 to 1.01±0.08 ng/dl, mean ± SEM;P<0.01). There was also a slight, but insignificant, elevation of thyroid stimulating hormone (TSH) in patients treated with minocycline. Similar suppression of thyroxine and free thyroxine was not observed in control patients treated with β-lactam and/or aminoglycoside antibiotics. Risk factors for the reduction in these thyroxine levels included age and a high serum baseline level of free thyroxine. We found a significant correlation between the free baseline thyroxine level and a reduction in free thyroxine after minocycline administration (Y=0.420X−0.377, r=0.597;P<0.01). Despite the observed alterations, the serum levels of all thyroid hormones after minocycline therapy were still within the normal range. This antibiotic does not appear to induce clinical hypothyroidism, yet given the results of this study, we would like to recommend pituitary-thyroid axis monitoring during the use of this antibiotic.

Effect of Probenecid on the Pharmacokinetics of DQ-2556, a New 3-Quaternary Ammonium Cephalosporin Antibiotic, in Humans

A total of 5 healthy volunteers were enrolled in a crossover study on the dose dependency and the effect of probenecid on pharmacokinetics of DQ-2556. They were administered intravenously 0.5 and 1.0 g of DQ-2556, and 1.0 g of DQ-2556 with oral administration of probenecid. The linearity in pharmacokinetics of DQ-2556 was confirmed up to the dose of 1.0 g. In the case of 1.0 g of DQ-2556 with probenecid treatment, the area under the serum concentration-time curve was larger, and total and renal clearances were less than those in the case of 1.0 g of DQ-2556 alone (by approximately 15% for each parameter, p < 0.01). These results demonstrated that DQ-2556 is secreted in the renal tubule, although it is excreted mainly by the glomerular filtration.

Drug Sensitivity Pattern of Gram-Negative Rod

It is well known to us all that antibiotics from the same group may differ in antimicrobial activity.