In vitro and in vivo determination of piperacillin metabolism in humans.
نویسندگان
چکیده
Piperacillin metabolism and biliary excretion are different between humans and preclinical species. In the present study, piperacillin metabolites were characterized in bile and urine of healthy humans and compared with metabolites formed in vitro. Volunteers were administered 2 g of piperacillin IV; blood, urine, and duodenal aspirates (obtained via a custom-made oroenteric catheter) were collected. The metabolism of piperacillin in humans also was investigated in vitro using pooled human liver microsomes and sandwich-cultured human hepatocytes. Piperacillin and metabolites were estimated by high-performance liquid chromatography with tandem mass spectrometry detection. Piperacillin, desethylpiperacillin, and desethylpiperacillin glucuronide were detected in bile, urine, and human liver microsomal incubates. Similar to the in vivo results, desethylpiperacillin was formed and excreted into bile canaliculi of sandwich-cultured human hepatocytes. This is the first report of glucuronidation of desethylpiperacillin in vitro or in vivo. The clinical method employed in this study to determine biliary clearance of drugs also facilitates bile collection as soon as bile is excreted from the gallbladder, thereby minimizing the exposure of labile metabolites to the intestinal environment. This study exemplifies how a combination of in vitro and in vivo tools can aid in the identification of metabolites unique to the human species.
منابع مشابه
The Role of Probiotics in Cancer Treatment: Emphasis on their In Vivo and In Vitro Anti-metastatic Effects
Probiotics are defined as live bacteria and yeasts that exert beneficial effects for health. Among their various effects, anti-cancer properties have been highlighted in recent years. Such effects include suppression of the growth of microbiota implicated in the production of mutagens and carcinogens, alteration in carcinogen metabolism and protection of DNA from oxidative damage as well as reg...
متن کاملThein vitro and in vivo Effect of Clinoptiloliteon Decreasing of Copper Ion and DNA Damage of Anodonta Cygnea
The ability of natural zeolite (Clinoptilolite) to remove copper from aqueous ecosystem was studied in real and laboratory conditions. Fresh water mussels (Anodonta Cygnea) of different sizes were Exposed to copper (150, 350, 450 µgl-1) for 10 days. Copper exposure induced DNA damage in the haemolymph cells of Anodonta of all sizes. In connection with real samples, the amount of damage and even...
متن کاملLinarin Inhibits the Acetylcholinesterase Activity In-vitro and Ex-vivo
Linarin is a flavone glycoside in the plants Flos chrysanthemi indici, Buddleja officinalis, Cirsium setosum, Mentha arvensis and Buddleja davidii, and has been reported to possess analgesic, antipyretic, anti-inflammatory and neuroprotective activities. In this paper, linarin was investigated for its AChE inhibitory potential both in vitro and ex vivo. Ellman’s colorimetric method was used for...
متن کاملEvaluation of γ-irradiation treatment on the antibacterial activities of Mentha piperita L. essential oils in vitro and in vivo systems (CLP inflammatory model)
Background: Mentha piperita L. essential oils have different antibacterial activity. In the present study, we investigated the effect of &gamma–irradiation on the antibacterial activities of Mentha piperita L. essential oils in vitro and in vivo systems. Materials and Methods: The aerial parts of peppermint were irradiated in a cobalt60 source with 0, 10 and 25 kGy absorbed doses. Then, t...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Drug metabolism and disposition: the biological fate of chemicals
دوره 35 3 شماره
صفحات -
تاریخ انتشار 2007