Drug administration Pharmacokinetics

U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER) and Center for Biologies Evaluation and Research (CBER). Guidance for Industry Population Pharmacokinetics. http //www.fda.gov/cder/guidance/1852fnl.pdf (accessed October 1,... 

Since 1999, when the Food and Drug Administration allowed the first health claim for soy-fortified foods in the USA, there has been a large increase in the sales of food products claiming to contain soy isoflavones. At the same time, over-the-counter supplements have become widely available. However, concerns have been raised about the real health benefits of such supplements in the absence of adequate information about bioavailability, pharmacokinetics and safety. To fill this gap, an extensive study on pure isoflavones and commercial soy isoflavone supplements has recently been carried out (Setchell et al, 2001). A selection of 31 commercially available supplements showed a wide variation in isoflavone composition and in the amount provided by one tablet. Furthermore, a lower isoflavone content, with respect to the claimed levels, has been observed in almost 50% of the analysed products. In one case, no isoflavones at all could be detected (Setchell et al, 2001). 

AG De Boer, F Moolenaar, LGJ de Leede, DD Breimer. Rectal drug administration clinical pharmacokinetic considerations. Clin Pharmacokinet 7 285-311, 1982. 

The single-dose toxicity studies were performed in two mammalian species, rat and mouse, by the route used in clinical practice, that is oral, as well as that ensuring adequate systemic exposure to the drug, that is intravenous. The subacute (3 months) toxicity studies were correctly carried out in the two animal species (rat, dog) in which also the pharmacokinetics was studied. Since in accordance with the International Conference on Harmonization (CPMP/ICH/286/95), 3-month toxicity studies support clinical trials for up to 1 month s duration (the longest duration of drug administration in clinical use), chronic toxicity studies have not been performed. 

Factors reported to influence TCA plasma concentrations include disease states (e.g., renal or hepatic dysfunction), genetics, age, cigarette smoking, and concurrent drug administration. Similarly, hepatic impairment, renal impairment, and age have been reported to influence the pharmacokinetics of SSRIs. 

The group of Byron and co-workers established an IPL model specifically to study drug deposition and absorption [14], and reported a novel technique for drug administration [15] and described the absorption of a variety of test compounds. The studies conducted in this model have been reviewed recently, along with a pharmacokinetic model developed to describe the disposition of the drugs administered via this route [119],... 

Borlak J, Blickwede M, Hansen T, Koch W, Walles M, Levsen K (2005) Metabolism of verapamil in cultures of rat alveolar epithelial cells and pharmacokinetics after administration by intravenous and inhalation routes. Drug Metab Dispos 33(8) 1108-1114... 

The experimental methods for evaluating the BRB transport in vivo and the ocular pharmacokinetics of systemic drug administration are relatively straightforward and have been in use for over two decades. Overall, they are useful as a guide for the selection of drug candidates for the treatment of retinal diseases. With the combined use of conventional in vivo methods and newly developed... 

Detailed pharmacokinetic investigations are a necessary prelude to the formal approval protocols of the Federal Drug Administration and its counterparts worldwide. Although this topic lies beyond the scope of this Hand-... 

The standard pharmacokinetic parameters of the compound such as a half-life or bioavailability cannot be reliably calculated, because the concentrations in plasma are below lOpg/mL. As analogously expected from the results on the shift in keto-alcohol equilibrium of 16,16-difluoro-PGE2, it is rapidly metabolized by C-15 reduction mediated by the ubiquitously expressed carbonyl reductase. The metabolism followed by jS-oxidation and co-oxidation forms a mixture of a and fi epimers at the 15-hydroxy moiety as a sole measurable metabolite [46], In 2006, the US Food and Drug Administration approved the drug application for an oral treatment of chronic idiopathic constipation in adults, estimating that 4-5 million Americans are affected. Lubiprostone has also completed a phase II trial in constipation-predominant irritable bowel syndrome, and has been further evaluated for other bowel dysfunctions. 

Rectal bioavailability and pharmacokinetics. Serenoa repens extract, administered rectally to 12 healthy male volunteers at a dose of 640 mg/person, produced the mean maximum concentration in plasma of nearly 2.60 (Xg/mL approx 3 hours after administration, with mean value for the area under the curve AUC 10 (Xg/hour/mL. The bioavailability and pharmacokinetic profile were similar to those observed after oral administration. T j occurred approx 1 hour later, and plasma concentration 8 hours after drug administration was still quantified. The drug tolerability was good, and no adverse effect was observed ". Serenoa repens capsules, administered orally at a dose of 160 mg four times daily or rectally 640 mg daily for 30 days to 60 patients with BPH, produced no significant differences in diminu-... 

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