Bioavailability effect

Pinheiro, J. P., Galceran, J. and van Leeuwen, H. P. (2003). Metal speciation dynamics and bioavailability. Effects of bulk depletion in biouptake, Environ. Sci. Technol., submitted. 

The design of crystallization processes for the manufacture of Active Pharmaceutical Ingredients is a significant technical challenge to Process Research and Development groups throughout the Pharmaceutical and related industries. It requires an understanding of both the thermodynamic and kinetic aspects of crystallization, to ensure that the physical properties of the product will consistently meet specification. Failure to address these issues may lead to production problems associated with crystal size, shape and solubility, and to dissolution and bioavailability effects in the formulated product. 

Macrolide Route of Protein Bioavailability Effect of food... 

When exposed to mixtures, chemicals in the exposure medium may affect each other s uptake by humans in a manner that is analogous to some of the bioavailability effects outlined here for environmental species. This was, for instance, shown for the neurotoxicity of EPN (O-ethyl-O-4-nitrophenyl phenylphosphono-thionate), which was enhanced by aliphatic hydrocarbons due in part to increased dermal absorption (Abou-Donia et al. 1985). It was also shown that dietary zinc inhibits some aspects of lead toxicity, which could in part be explained by decreasing dietary lead absorption (Cerklewski and Forbes 1976). Other examples of interactions of chemicals at the uptake phase in humans, which may in part be related to bioavailability interactions, are summarized in Table 1.3. 

A decision whether or not the substance be classified will be made by comparing aquatic toxicity data and solubility data. If the L(E)Cso is exceeded, irrespective of whether the toxicity and dissolution data are at the same pH and if this is the only data available then the substance should be classified. If other solubility data are available to show that the dissolution concentration would not exceed the L(E)C5o across the entire pH range then the substance should not be classified on its soluble form. This may involve the use of additional data either from ecotoxicological testing or from applicable bioavailability-effect models. 

Smolen, V. F., Turrie, B. O., Weigand, W. A. Drug input optimization Bioavailability-effected time-optimal control of multiple, simultaneous, pharmacological effects and their interrelationships. J. Pharm. Sci. 61, 1941 (1972). 

Apply biological methods capable of accurate assessment of ecological effects that integrate mixture and bioavailability effects. 

Gidal BE, DeCerce J, Bockbrader HR, et al. Gabapentin bioavailability Effect of dose and frequency of administration in adult patients with epilepsy. Epilepsy Res 1998 31 91-99. 

Abernethy DR, Divoll M, Greenblatt DJ, Shader RI. Imipramine pharmacokinetics and absolute bioavailability effect of food ClinRes (1983) 31, 626A,... 

One of the most popular orally active penicillins in present clinical use is amoxicillin (12). Its oral effectiveness and broad spectrum of activity against common pathogens as well as its better absorption than its closest precedent competitor, ampicillin (14), largely accounts for this. Higher blood and tissue levels of antibiotics is another means of dealing with resistance. In an attempt to achieve yet further improvements in oral bioavailability and hence blood and ti.ssue levels of amoxicillin, the prodmg fumoxicillin (13) is prepared from amoxicillin (12) by treatment with furfural [3]. The imine moiety is less basic than the primary amine so that the isoelectric point of fumoxicillin is more on the acid side than is that of amoxicillin. 

The separation of enantiomers is a very important topic to the pharmaceutical industry. It is well recognized that the biological activities and bioavailabilities of enantiomers often differ [1]. To further complicate matters, the pharmacokinetic profile of the racemate is often not just the sum of the profiles of the individual enantiomers. In many cases, one enantiomer has the desired pharmacological activity, whereas the other enantiomer may be responsible for undesirable side-effects. What often gets lost however is the fact that, in some cases, one enantiomer may be inert and, in many cases, both enantiomers may have therapeutic value, though not for the same disease state. It is also possible for one enantiomer to mediate the harmful effects of the other enantiomer. For instance, in the case of indacrinone, one enantiomer is a diuretic but causes uric acid retention, whereas the other enantiomer causes uric acid elimination. Thus, administration of a mixture of enantiomers, although not necessarily racemic, may have therapeutic value. 

Most ACE inhibitors are prodrugs, with the exceptions of captopril, lisinopril, and ceranapril. Prodrugs exert improved oral bioavailability, but need to be converted to active compounds in the liver, kidney, and/or intestinal tract. In effect, converting enzyme inhibitors have quite different kinetic profiles with regard to half time, onset and duration of action, or tissue penetration. 

The dopamine precursor l-DOPA (levodopa) is commonly used in TH treatment of the symptoms of PD. l-DOPA can be absorbed in the intestinal tract and transported across the blood-brain barrier by the large neutral amino acid (LNAA) transport system, where it taken up by dopaminergic neurons and converted into dopamine by the activity of TH. In PD treatment, peripheral AADC can be blocked by carbidopa or benserazide to increase the amount of l-DOPA reaching the brain. Selective MAO B inhibitors like deprenyl (selegiline) have also been effectively used with l-DOPA therapy to reduce the metabolism of dopamine. Recently, potent and selective nitrocatechol-type COMT inhibitors such as entacapone and tolcapone have been shown to be clinically effective in improving the bioavailability of l-DOPA and potentiating its effectiveness in the treatment of PD. 

Diclofenac is an exceedingly potent COX inhibitor slightly more efficacious against COX-2 than COX-1. Its absorption from the gastrointestinal tract varies according to the type of pharmaceutical formulation used. The oral bioavailability is only 30-80% due to a first-pass effect. Diclofenac is rapidly metabolised (hydroxylation and conjugation) and has a plasma half-life of 1.5 h. The metabolites are excreted renally and via the bile. 

Recently, leaders in the pharmaceutical industry have developed a list of desired properties for a fourth generation of SERMs (Table 2). In general, future SERMs must oppose endogenous hormone action in the breast and reproductive system while displaying full estrogenic effects in the cardiovasculature, bone and central nervous systems. Additional criteria are that fourth generation compounds possess superior bioavailability compared with existing SERMs and have... 

Co-administration of ofloxacin and chitosan in eyedrops increased the bioavailabUity of the antibiotic [290]. Trimethyl chitosan was more effective because of its solubility (plain chitosan precipitates at the pH of the tear fluid). On the other hand, N-carboxymethyl chitosan did not enhance the corneal permeability nevertheless it mediated zero-order ofloxacin absorption, leading to a time-constant effective antibiotic concentration [291]. Also W,0-carboxymethyl chitosan is suitable as an excipient in ophthalmic formulations to improve the retention and the bioavailability of drugs such as pilocarpine, timolol maleate, neomycin sulfate, and ephedrine. Most of the drugs are sensitive to pH, and the composition should have an acidic pH, to enhance stability of the drug. The delivery should be made through an anion exchange resin that adjusts the pH at around 7 [292]. Chitosan solutions do not lend themselves to thermal sterilization. A chitosan suspension, however. 

Among the physical factors, current velocity has a special significance for benthic biofilms because it can modulate the diffusion of metals through the biofilm and their effects [18, 40]. pH and organic complexation are particularly significant for metal bioavailability [42]. Therefore, metal toxicity will also depend on the influence that environmental variability has on its bioavailability. 

Toluene, volatile nitrites, and anesthetics, like other substances of abuse such as cocaine, nicotine, and heroin, are characterized by rapid absorption, rapid entry into the brain, high bioavailability, a short half-life, and a rapid rate of metabolism and clearance (Gerasimov et al. 2002 Pontieri et al. 1996, 1998). Because these pharmacokinetic parameters are associated with the ability of addictive substances to induce positive reinforcing effects, it appears that the pharmacokinetic features of inhalants contribute to their high abuse liability among susceptible individuals. 

Polymeric microparticles have been studied and developed for several years. Their contribution in the pharmacy field is of utmost importance in order to improve the efficiency of oral delivery of drugs. As drug carriers, polymer-based microparticles may avoid the early degradation of active molecules in undesirable sites of the gastrointestinal tract, mask unpleasant taste of drugs, reduce doses and side effects and improve bioavailability. Also, they allow the production of site-specific drug targeting, which consists of a suitable approach for the delivery of active molecules into desired tissues or cells in order to increase their efficiency. 

---