Expert opinion on drug metabolism & toxicology
-
Expert Opin Drug Metab Toxicol · Feb 2011
ReviewMethylnaltrexone bromide: research update of pharmacokinetics following parenteral administration.
Opioid-induced constipation is a major side effect of the use of opioid pain medications in a palliative care population. At present, the only approved treatment for opioid-induced constipation is methylnaltrexone bromide subcutaneous injection. Methylnaltrexone is a peripherally restricted opioid antagonist with μ-opioid receptor selectivity that can reduce opioid activity in peripheral organs such as the gastrointestinal tract while sparing the pain relief afforded by the pain medications. ⋯ Studies conducted to date indicate that methylnaltrexone has high bioavailability after subcutaneous administration at therapeutic dose levels, a terminal half-life of ∼ 8 - 9 h, minimal metabolism, elimination involving renal and non-renal routes, and a limited potential for drug-drug interactions. Combined with high efficacy and good tolerability, the predictable pharmacokinetic behavior of methylnaltrexone facilitates its successful utilization in clinical practice for the treatment of opioid-induced constipation in patients with advanced medical illness.
-
Although colistin has recently played a key role in the treatment of nosocomial infections due to multidrug resistant Gram-negative pathogens, there is a lack of clinical studies examining colistin pharmacokinetics (PKs) in humans. This refers to all routes of colistin administration in clinical practice. Colistin PK data are also limited in critically ill patients. ⋯ There is a lack of human studies on colistin PK and PD. Significant PD parameters best predicting colistin efficacy and their optimal values such as C(max):MIC ratio, AUC/MIC and T > MIC have not yet been clearly defined. It should be noted that further investigation on colistin PK/PD in vitro and in vivo models is required.