Therapeutic activity

The therapeutically active dmg can be extracted from plant or animal tissue, or be a product of fermentation (qv), as in the case of antibiotics. Frequentiy, it is synthesized and designed to correlate stmcture with therapeutic activity. Pharmacologic activity is first tested on laboratory animals. When the results ate encouraging, physical and chemical properties are determined in the so-called preformulation stage, and analytical procedures are developed for quahty control (see Qualityassurance/qualitycontrol). 

Pharmacokinetics is the study of how the body affects an adiriinistered dmg. It measures the kinetic relationships between the absorption, distribution, metaboHsm, and excretion of a dmg. To be a safe and effective dmg product, the dmg must reach the desired site of therapeutic activity and exist there for the desired time period in the concentration needed to achieve the desired effect. Too Htde of the dmg at such sites yields no positive effect ( MTC) leads to toxicity (see Fig. 1). For intravenous adininistration there is no absorption factor. Total body elimination includes both metabohc processing and excretion. 

Dosage forms of naturally occurring materials having therapeutic activity are prepared by extractive processes, especially percolation and maceration. Examples of such dosage forms have included certain tinctures, symps, fluid extracts, and powdered extracts. 

Intravenous aqueous injections provide an excellent means of achieving a rapid therapeutic response. Parenteral product design, eg, vehicle and other excipient selection, as well as choice of route of adrninistration, can prolong therapeutic activity and increase onset times. Thus, oily solutions, suspensions, or emulsions can be adrninistered by subcutaneous or intramuscular routes to create prolonged effect, ie, depot injection (28). 

Sulfonamides derived from sulfanilamide (p-arninoben2enesulfonainide) are commonly referred to as sulfa dmgs. Although several dmg classes are characterized by the presence of a sulfonamide function, eg, hypoglycemics, carbonic anhydrase inhibitors, saluretics, and tubular transport inhibitors, the antibacterial sulfonamides have become classified as the sulfa dmgs. Therapeutically active derivatives are usually substituted on the N nitrogen the position is generally unsubstituted. These features are illustrated by the stmctures of sulfanilamide (1) and sulfadiazine (2)... 

In Vivo Properties. The efficacy of dalbaheptides has been assessed ia various models of experimental septicemia ia mice. In general there was good correlation between the ED qS (effective doses which prevent death ia 50% of test animals) and the MICs on test strains. Teicoplanin was very effective, ED q values ranged from 0.11 to 0.72 mg/kg sc administration for septicemias caused by S. pyogenes S. pneumoniae and S. aureu whereas for vancomycin ED qS were from 0.58 to 7.2 mg/kg (33). Eremomycin (52) had therapeutic activity 2—3 times greater than vancomycin. Therapeutic indices... 

There are no hiUy effective therapeutic agents for the treatment of thederiasis. Chlorotetracycline (20) and oxytetracycline (3) have therapeutic activity duting the iacubation period. Pamaquiae (68) was reported to have a specific effect on the erythrocyctic forms. Other dmgs with limited efficacy are imidocarb (19) on T annulata halofugiaone (45) on both T annulata and T parva and the naphthoquiaones menoctone (76), parvaquone (88), and buparvaquone (89) on T parva. Methotrexate (90) has been found to be active in vitro (Table 9). 

A major consideration in screening is the detection capability of the screen for both false negatives (lack of detection of an active drug) and propensity to find false positives (detection of a response to the compound not due to therapeutic activity of interest). Ostensibly, false positives might not be considered a serious problem in that secondary testing will detect these and they do not normally interfere with the drug discovery process. 

Another type of therapeutically active molecule is one designed primarily with pharmacokinetics in mind (designed to be well absorbed and to enter the central compartment readily), which can then be converted to the therapeutically active molecule in the body. These are referred to as pro-drugs. This process, called latentiation, consists of the conversion of hydrophilic drugs into lipid-soluble drugs (usually by masking hydroxyl, carboxyl, and... 

An added complexity, but one that may better predict therapeutic activity, is the testing of drugs in assays with different contexts (i.e., basal stimulation). 

Based on the role of endocannabinoids and cannabinoid receptors in several pathological conditions, the pharmacological manipulation of their levels or action is being developed as a therapeutic strategy. Enhancement of endocannabinoid signalling when this plays uniquely a protective role can be effected in a safer way using (i) cannabis extracts in which the presence of non-psychotropic cannabinoids with therapeutic activity per... 

Use of the macrolides increases serum levels of digoxin and increases the effects of anticoagulants. Use of antacids decreases the absorption of most macrolides. The macrolides should not be administered with clindamycin, lincomycin, or chloramphenicol a decrease in the therapeutic activity of the macrolides can occur. Concurrent administration of the macrolides with theophylline may increase serum theophylline levels. 

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