Activity pharmacodynamics

This hypothesis clearly contradicted a large body of clinical evidence that nitrates were effective. Some years later, using more sensitive and reliable analytical methods, this interpretation was shown to be incorrect, and the clinical utility of long-acting, oral organic nitrate derivatives affirmed. In 1967, one of the pharmacodynamically active metabolites of ISDN, IS-5N, was shown to be formed in vivo, and shortly thereafter it was introduced as a novel long-acting NO donor with improved bioavailability. 

Piperacillin- tazobactam In vitro anti-infective effect of piperacillin-tazobactam (PIP-TZB) combinations on Escherichia coli showed through a PK/PD model that for these combinations, three-times-a-day administration is as effective as four times a day. Pharmacodynamic activity of the combinations can be prolonged by sufficiently high inhibitor concentrations... 

Donepezil is well absorbed with a relative oral bioavailability of 100% and reaches peak plasma concentrations in 3-4 h. Oral administration of Aricept produces highly predictable plasma concentrations with plasma concentrations and area under the curve rise in proportion to the dose. The terminal disposition half-life is approximately 70 h, thus administration of multiple single-daily doses results in gradual approach to steady state. Approximate steady state is achieved within 3 weeks after the initiation of therapy. Once at steady state, plasma donepezil hydrochloride concentrations and the related pharmacodynamic activity show little variability over the course of the day. Neither food nor time of administration (morning versus evening dose) affect the absorption of donepezil hydrochloride [46-51]. 

Ideally biomarkers of activity should be identified at various times over the course of the study to support the pharmacodynamic activity (e.g., normalization of insulin, improvement in beta cell function as measured by C-peptide level, or control of glucose following transplantation of P pancreatic islet cells) improvement of motor coordination in mice with spinal cord damage following transplant of neurons or repair of heart function (e.g., functional measures such as LV ejection fraction, pressure volume loops, ventricular pressure and heart wall thickness). Such markers may also be useful in subsequent clinical... 

All ergot alkaloids which have so far been used therapeutically are lysergic acid derivatives. Representatives of the second main group, the clavine alkaloids, have also been found to be pharmacodynamically active, but as yet, none has been found to exert effects that can be utilized in therapy. The uterotonic and sympatholytic actions are less prominent in their pharmacological spectra of activity but, for example, elymoclavine and agroclavine have a pronounced central excitatory action which is attributed to their stimulation of sympathetic centers (172). 

Pharmacological tests have shown that the substituent in position 2 produces an exaltation of the pharmacodynamic activity. These compounds have been claimed to be nervous system depressants, in particular with sedative, antiepileptic, and tranquilizing activity.100-105 Spasmolytic activity was shown by phenoxazine-10-carboxylic106 or phenoxazine-10-dithiocarboxylicalkylamino esters,78... 

As with morphine and the benzomorphans, variation of the N-substituent (Chapters 2 and 4) markedly affects opioid pharmacodynamic activity, and (—) 49 (R = OH R = allyl) known as levallorphan or Lorphan is an antagonist several times more potent than nalorphine. Rather than prepare levallorphan by the N-demethylation 49, (R = OH R = Me) and allylation, on a commercial scale 51 (R and R = H) or 51 (R = H R = CH2C6H5) are obtained optically pure.(34) The former may be allylated and cyclized, whereas the latter was cyclized, debenzylated by hydrogenolysis, and finally converted to levallorphan with allyl bromide. 

The pharmacodynamically active molecular structure of the calcium channel blocker, nifedipine, is photodecomposed by UV-VIS radiation (8). This effect is manifested by a change in color (from yellow to colorless) or the fading of colored preparations, formation of precipitation and alteration of the taste of the product. Such changes during storage may give patients the sense of uneasiness, confusion, and doubt as to the safety and efficacy of the product. 

A relationship between pharmacokinetic data and pharmacodynamic activity is assumed. There is no interest in predicting variations in plasma concentration using a correlation if these have no measurable influence on pharmacodynamic and pharmacological activity, and therefore none on therapeutic effectiveness. In addition the moiety responsible of the therapeutic activity must be known. 

The 2-arylpropionic acid ( profen ) non-steroidal anti-inflammatory drugs, each of which contains a single chiral center, are formulated as racemic (50 50) mixtures of the S(+)- and R(-)-enantiomers, with the exception of naproxen, which is formulated as the S(- -)-enantiomer. Based on inhibition of cyclooxygenase activity, the S(- -)-enantiomer is the eutomer (more potent enantiomer). These drugs differ markedly in both pharmacodynamic activity and pharmacokinetic behavior and, in addition, enantiomer pharmacokinetics of each drug varies among animal species. After intravenous administration of racemic keto-profen to horses, sheep, and 20-week-old calves and measurement of individual enantiomers in plasma, significant differences between the enantiomers were found in systemic clearance in horses and in both systemic clearance and volume of distribution in sheep... 

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