Pharmacologically active substances

Applications to establish MRLs for new pharmacologically active substances must be submitted to the European Medicines Agency (EMEA) at least 6 months in advance of an application for a marketing authorisation. In order to avoid delays, manufacturers are advised to submit an application once all the necessary data are available, as a product authorisation carmot be granted unless established MRLs are in place. The EMEA should be notified of the intent to submit an application 3 to 4 months in advance of the anticipated date, so that a Rapporteur and Co-Rapporteur can be appointed from among the members of the Committee for Veterinary Medicinal Products (CVMP). 

Many, if not most, pharmacologically active compounds are amines. For this reason, issues in the RPLC of substances of pharmaceutical interest tend to be similar to those encountered in the separation of amines. Incompletely endcapped silica-based phases may exhibit tailing. The use of ion pairing or ion suppression is common in the analysis of pharmacologically active substances. Also, derivatization of the amine functionality prior to analysis may be required. The RPLC retention indices of most common pharmaceutical compounds have been compiled.97... 

Tmovec, T., Z. Kallay, and S. Bezek. 1990. Effects of ionizing radiation on the blood brain barrier permeability to pharmacologically active substances. Inter. Jour. Radiation Oncol. Biol. Physics 19 1581-1587. 

Large quantities of pharmacologically active substances are used annually in human medicine for diagnosis, treatment, and prevention of illness or to avoid unwanted pregnancy. In animal and fish farming, drugs are mostly adminis-... 

A core activity of the CVMP is the establishment of MRLs of veterinary medicinal products permissible in food produced by or from animals for human consumption, including dairy products, meat, honey, etc. These limits must be established for all pharmacologically active substances contained in a medicinal product before the product can be granted a marketing authorization. 

The preparation of barbiturates illustrates many of the synthetic methods covered in this chapter. The preparation employs the reaction of urea (C0(NH2)2) with malonic ester to form barbituric acid. The general reaction is presented in Figure 15-30. The stable pyrimidine and other resonance forms help drive the reaction. By alternating the substituent at carbon number five (C5), various pharmacologically active substances can be formed. Barbital, a sedative, and phenobarbital, a sleeping aid, are shown in Figure 15-31. 

A Aumatell, RJ Wells. Enantiomeric differentiation of a wide range of pharmacologically active substances by cyclodextrin-modified micellar electrokinetic capillary chromatography using a bile salt. J Chromatogr A 688 329—337, 1994. 

In accordance with these regulations, the Commission has published a timetable for the consideration of establishing MRLs for substances currently authorized for use in food-producing animals, including time limits for submission of hre relevant information by the sponsors. Information and particulars to be included in an apphcation for the establishment of MRLs for a pharmacologically active substance used in veterinary medicinal products are provided in the 2311 90/EEC Regulation. It is essential for this application to contain two particular documentation files the safety and the residue files. 

By now, MRL values have been established for many pharmacologically active substances as shown in Table 11.6. It is expected, however, that with the start of the new century all active substances intended for use in food-producing animals will be listed in one of the Annexes I—III of the amendments of the regulation 2377/90/EEC if not, their administration to animals will be prohibited. 

Annex I contains the list of pharmacologically active substances in respect of which MRLs have been established. Entry into Annex I depends on full packages of toxicological and residue data, the analysis of which suggests no major human health concerns. 

Pci-Gen, X. and Shan-Li, F., Pharmacologically active substance of Chinese traditional and herbal medicines, in Herbs, Spices, and Medicinal Plants Recent Advances in Botany, Horticulture, and Pharmacology, Vol. 2, Craker, L.E. and Simon, J.E., Eds., Food Products Press, New York, 1991, 1-55. 

The collapse of the networks was studied experimentally mainly for the case of mixed solvents. From the practical point of view, it would be interesting to generate the collapse in a purely aqueous medium. In this case, by changing the interactions between subchains of the network in aqueous solution it is possible, for example, to influence effectively diffusion in gels that are used as carriers of enzymes or pharmacologically active substances. One of the new directions in the research of network polymers is the study of their interaction with linear macromolecules. The results of the theoretical analysis of the behavior of polymer networks swollen in polymer solutions have been discussed in Ref. [34,35] (see Sect. 2.4.2). 

Table 7 gives some examples where several pharmacologically active substances were linked to polysaccharides forming complexes of pharmaceutical interest. They are of remarkable chemical stability and resistence to decomposition at higher... 

Endo M, Nakagawa M, Hamamoto Y, Ishihama M (1986) Pharmacologically Active Substances from Southern Pacific Marine Invertebrates. Pure Appl Chem 58 387... 

Often an active drug is converted to another pharmacologically active substance. The following table lists a few examples of this. 

Annex I Pharmacologically active substances for which an MRL has been fixed... 

Annex II Substances not subject to a maximum residue limit Annex III Pharmacologically active substances used in veterinary medicine for which a provisional maximum residue limit has been fixed Annex IV Pharmacologically active substances for which no maximum residue limit can be fixed. 

Lanolin has been used for many years as a vehicle for pharmacologically active substances in ophthalmic ointments and topical formulations.55-60 In addition to being a vehicle for penicillin and other antimicrobial substances, lanolin contains lipids such as 10-methyldodecanoic acid and 12-methyltridecanoic acid, which have antimicrobial activity.61,62... 

This possibility of intimate association of rhodium with the aromatic ring suggests further experiments. A logical extension of asymmetric syntheses involving prochir-al reactants is a kinetic resolution with related chiral reactants under similar conditions. In the one case of hydroboration-amination where this has been applied, it has proved to be very effective. The reactant was prepared directly by a Heck reaction on 1,2-dihydronaphthalene, and under the standard conditions of catalytic hydrobora-tion gave >45% of both enantiomerically pure recovered alkene with (after oxidative work-up) the alcohol of opposite hand, mainly as the trans-isomer. This procedure forms a simple and potentially useful route to pharmacologically active substances, demonstrated by the racemic synthesis shown [105] (Scheme 34). 

Fennel contains anethole, an antispasmatic, along with other pharmacologically active substances. The various scientifically documented medicinal effects of fennel are listed below. 

Cells by themselves or by secreting pharmacologically active substances may have effects on the CNS, cardiac, respiratory, renal, or GI systems. Safety pharmacology should therefore be considered on a case-by-case basis depending on the specific characteristics of the cell-based product [52], In general, specific assessments are made as part of the toxicology assessments rather than as stand-alone studies consistent with the assessments made with protein-based biopharmaceuticals [50]. The fundamental physiological differences (e.g., total blood volume,pulmonary capillary surface area, and volume) should... 

Candesartan cilexetil (converted to candesartan), olmesartan medoxomil (converted to olmesartan) and losartan (converted to EXP-3174 which is 10- to 40-times more potent than losartan) are prodrugs. While losartan is a reversible, surmountable competitive inhibitor, EXP-3174 is a reversible noncompetitive inhibitor of the AT, receptor therefore, losartan may compete for the same receptor. All other ARBs are pharmacologically active substances. Losartan requires a 50% initial dose reduction in patients with impaired hepatic function [21]. All agents can be dosed once daily, and telmisartan has the longest plasma half-life. 

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