To elucidate the mechanism of the BDL-induced increase, we analyzed the effect of BDL on intestinal flora in wild type and inducible nitric oxide synthase (iNOS)-deficient mice (iNOS(-/-)) using the terminal restriction fragment length polymorphism analysis (T-RFLP) and 165 rDNA clone libraries. The amounts of bacterial DNA detected in fecal samples from both animal groups pretreated

with antibiotics were extremely low as compared with untreated groups. We found that the profiles of enteric bacteria changed markedly after BDL. The bacterial composition is significantly different between not only wild JQ-EZ-05 cell line type and iNOS(-/-) mice but also those before and after BDL, respectively. Among enteric bacteria examined, Lactobacillus marinas was found to increase markedly after BDL in rectum of both animal groups. However, Escherichia coli markedly increased after BDL in the iNOS(-/-) mice. These findings suggest that profiles of enteric flora change markedly in animals during obstructive jaundice by some mechanism that is affected by bile constituents and iNOS-derived NO.”
“Objective:

The transdermal therapeutic system (TTS) with buprenorphine is currently being used ‘off-label’ to treat chronic pediatric pain. We compiled available pharmacokinetic (PK), pharmacodynamic (PD), and clinical pediatric data on buprenorphine to rationalize ASP2215 treatment regimens.

Methods: We conducted a systematic biomedical literature review focusing on pediatric buprenorphine data.

Results:

There are few relevant pediatric buprenorphine data, particularly in children suffering chronic pain. There are no pediatric PK and PD data for children with chronic pain given sublingual or TTS formulations. Children given single dose buprenorphine have increased drug clearance referenced to bodyweight with a possible paradoxical longer duration of action. Buprenorphine metabolism is independent of renal function, which is advantageous in renal insufficiency. The risk of respiratory depression after buprenorphine is difficult to quantify. A concentration-response BMS-754807 concentration relationship for respiratory effects has not been described and it is unknown whether children have a ceiling effect similar to that described in healthy adult volunteers.

Conclusions: Buprenorphine is of interest in pediatric postoperative pain and cancer pain control because of its multiple administration routes, long duration of action, and metabolism largely independent of renal function. There is little reason to expect buprenorphine effects in children out of infancy are fundamentally different to those in adults. From the limited pediatric data available, it appears that buprenorphine has no higher adverse potential than the more commonly used opioids. There is an urgent need for focused PK, PD, and safety studies in children before use in children becomes more widespread.