Pharmacodynamic profiles

Pharmacokinetic profile Pharmacodynamic profile Bioequivalence and bioavailability Acute toxicity Chronic toxicity... 

Establish a dose-response pharmacodynamic profile by using initial doses projected to be therapeutic in humans. The dose required is predicted on the basis of blood levels found in animal screens. 

The metabolism of heroin is of interest in connection with its pharmacological activities. Earlier opiate -receptor binding studies led to the belief that heroin is a prodrug acting through its metabolites 6-acetylmorphine and morphine [95]. However, heroin is now known to activate (5-receptors, whereas morphine activates -receptor and 6-acetylmorphine acts at both receptor types [96]. Thus, the pharmacodynamic profile of heroin results from both direct and metabolite-mediated effects. 

Wienrich M, Meier D, Ensinger HA, Pharmacodynamic profile of the M-1 agonist talsaclidine in animals and man, Life Sci 22 2593-2600, 2001. 

Concomitant disease states, concurrent medications, or other factors likely to alter the pharmacokinetic or pharmacodynamic profile of digoxin. 

Vaira V, Fedele G, Pyne S et al (2010) Preclinical model of organotypic culture for pharmacodynamic profiling of hmnan tumors. Proc Natl Acad Sci USA 107 8352-8356... 

Comprehensive knowledge of the clinical pharmacology (e.g., concentration-effect relationships, pharmacokinetic and pharmacodynamic profile, information related to altered drug disposition and/or action consequent to development, disease, concomitant drug therapy) for the drug(s) of interest... 

Nebivolol is a new selective adrenergic blocking agent that possesses a unique pharmacodynamic profile, by which it differs from traditional P -blockers. 

Substantially different pharmacodynamic profiles from earlier MAOIs... 

The general pharmacology of the barbiturates is discussed in Chapter 22. Thiopental is a barbiturate commonly used for induction of anesthesia. Thiamylal is structurally almost identical to thiopental and has the same pharmacokinetic and pharmacodynamic profile. 

When insulin lispro and insulin aspart were compared in a single-blind, randomized, crossover study in 14 patients with type 1 diabetes, insulin lispro had a faster onset of action but a shorter duration (11). However, in another study the pharmacokinetic and the pharmacodynamic profiles of insulin aspart compared with human insulin were the same in 24 healthy Japanese as in non-Japanese (12). Insulin aspart and insulin lispro were equally effective in another 24 patients with type 1 diabetes (13). 

Unithiol has no FDA-approved indications, but experimental studies and its pharmacologic and pharmacodynamic profile suggest that intravenous unithiol offers advantages over intramuscular dimercaprol or oral succimer in the initial treatment of severe acute poisoning by inorganic mercury or arsenic. Aqueous preparations of unithiol (usually 50 mg/mL in sterile water) can be administered at a dose of 3-5 mg/kg every 4 hours by slow intravenous infusion over 20 minutes. If a few days of treatment are accompanied by stabilization of the patient s cardiovascular and gastrointestinal status, it may be possible to change to oral administration at a dose of 4-8 mg/kg every 6-8 hours. Oral unithiol may also be considered as an alternative to oral succimer in the treatment of lead intoxication. 

In general, the efficacy of hypnotics for short-term use is well established and there is a close relationship between their pharmacokinetic and pharmacodynamic profiles. The most widely used hypnotic in the UK, for example, is temazepam, which is relatively slowly absorbed and therefore has only a marginal effect on the sleep latency but facilitates sleep duration. 

The most serious complication of neuraxial block (epidural or spinal anesthesia) is spinal hematoma with resulting paraplegia, Based on the pharmacokinetic and pharmacodynamic profile of... 

Large interindividual dosing differences Predictable and reproducible pharmacokinetic and pharmacodynamic profile... 

Post JM, Sullivan ME, Abendschein D, et al. Human in vitro pharmacodynamic profile of the selective Factor Xa inhibitor ZK-807834 (Cl-103 I). Thromb Res 2002 105 347-352. 

In this context, other approaches have been developed to improve the pharmacokinetic and pharmacodynamic properties of recombinant proteins in vivo. These have included the addition of polyethylene glycol to the recombinant molecules (PEGyla-tion) and the use of sustained-release delivery systems. One goal of these approaches is to achieve clinical efficacy and lower the number of administrations, possibly to single injections, and thereby increase patient compliance. In addition to improving the pharmacokinetic and pharmacodynamic profile of recombinant molecules, sustained release may also increase the biological activity of specific molecules. 

Herling AW, Burger HJ, Schwab D et al. (1998) Pharmacodynamic profile of a novel inhibitor of the hepatic glucose-6-phosphatase system. Am J Physiol 274 G1087-G1093... 

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