Therapeutic concentration

Disopyr mide. Disopyramide phosphate, a phenylacetamide analogue, is a racemic mixture. The dmg can be adininistered po or iv and is useful in the treatment of ventricular and supraventricular arrhythmias (1,2). After po administration, absorption is rapid and nearly complete (83%). Binding to plasma protein is concentration-dependent (35—95%), but at therapeutic concentrations of 2—4 lg/mL, about 50% is protein-bound. Peak plasma concentrations are achieved in 0.5—3 h. The dmg is metabolized in the fiver to a mono-AJ-dealkylated product that has antiarrhythmic activity. The elimination half-life of the dmg is 4—10 h. About 80% of the dose is excreted by the kidneys, 50% is unchanged and 50% as metabolites 15% is excreted into the bile (1,2). 

Mexifitene is well absorbed from the GI tract and less than 10% undergoes first-pass hepatic metabolism. In plasma, 60—70% of the dmg is protein bound and peak plasma concentrations are achieved in 2—3 h. Therapeutic plasma concentrations are 0.5—2.0 lg/mL. The plasma half-life of mexifitene is 10—12 h in patients having normal renal and hepatic function. Toxic effects are noted at plasma concentrations of 1.5—3.0 lg/mL, although side effects have been noted at therapeutic concentrations. The metabolite, /V-methy1mexi1itene, has some antiarrhythmic activity. About 85% of the dmg is metabolized to inactive metabolites. The kidneys excrete about 10% of the dmg unchanged, the rest as metabolites. Excretion can also occur in the bile and in breast milk (1,2). 

EoUowing po administration moricizine is completely absorbed from the GI tract. The dmg undergoes considerable first-pass hepatic metabolism so that only 30—40% of the dose is bioavailable. Moricizine is extensively (95%) bound to plasma protein, mainly albumin and a -acid glycoprotein. The time to peak plasma concentrations is 0.42—3.90 h. Therapeutic concentrations are 0.06—3.00 ]l/niL. Using radiolabeled moricizine, more than 30 metabolites have been noted but only 12 have been identified. Eight appear in urine. The sulfoxide metabolite is equipotent to the parent compound as an antiarrhythmic. Elimination half-life is 2—6 h for the unchanged dmg and known metabolites, and 84 h for total radioactivity of the labeled dmg (1,2). 

This synopsis refers only to actions demonstrated within or close to therapeutic concentrations of drugs. Abbreviations (+) to (+++) weak to strong efficacy, (-) no efficacy, ( ) not investigated. HVA high threshold Ca2 channels, T T-type Ca2+ channels, L L-type Ca2+ channels, iNap persistent sodium current, DR delayed rectifier K channels, KCNQ KCNQ subtypes of K+ channels. 

Cardiac glycosides have a small ratio of toxic to therapeutic concentration. Possible adverse effects are nausea, vomiting, abdominal pain, diarrhoea, fatigue, headache, drowsiness, colour vision disturbances, sinus bradycardia, premature ventricular complexes, AV-block, bigeminy, atrial tachycardia with AV-Block, ventricular fibrillation. There are several mechanisms relevant for their toxic action (Table 2). 

In noncancer-related pharmacology, GSK3 is inhibited by lithium at therapeutic concentrations, implying that the long-established effectiveness of lithium in the treatment of psychiatric mood disorders (and more recently as a neuroprotective agent) may be linked to GSK3 inhibition. Antipsychotics such as haloperidol... 

Penicillin is the dmg of choice for the treatment of group B streptococcal, meningococcal and pneumococcal infections but, as discussed earlier, CSF concentrations of penicillin are significantly influenced by the intensity of the inflammatoiy response. To achieve therapeutic concentrations within the CSF, high dosages are required, and in the case of pneumococcal meningitis should be continued for 10-14 days. 

PET studies show that at effective therapeutic plasma concentrations most neuroleptics occupy some 80% of brain Dj receptors (in the striatum at least) and this is therefore considered to be a requirement for efficacy (Pilowsky, Costa and Eli 1992 Farde 1996). If that is so then clozapine, which occupies only 20-40% of the Dj receptors at a therapeutic concentration, must have some other action which accounts for its therapeutic effectiveness. 

Among the D2 family of receptors (D2, D3 and D4) the D2 receptor itself seems to be the most important. At a therapeutic concentration, most neuroleptics, except clozapine (and risperidone), should, according to in vitro binding studies, be occupying 50-70% of brain D2 receptors. The picture is similar for D3 receptors but only clozapine (and... 

Usually, one has obtained an estimate for the elimination constant and the distribution volume Vp from a single intravenous injection. These pharmacokinetic parameters, together with the interval between administrations 0 and the single-dose D, then allow us to compute the steady-state peak and trough values. The criterion for an optimal dose regimen depends on the minimum therapeutic concentration (which must be exceeded by and on the maximum safe... 

Vancomycin Infusion related toxicity (phlebitis, red man syndrome) Potential for additive renal toxicity if being coadministered with a nephrotoxic agent (e.g., aminoglycoside) monitor renal function (BUN/SCr) weekly in stable patients Consider vancomycin troughs to ensure therapeutic concentrations ... 

Studies have found that administration of the antimicrobial should begin as close to the first incision as possible. This is important for antibiotics with short half-lives so that therapeutic concentrations are maintained during the operation and reduce the need for redosing. Beginning the infusion after the first incision is of little value in preventing SSL Stone and associates found that administration of the antimicrobial after the first incision had SSI rates similar to patients who did not receive prophylaxis.20... 

In addition to desiring therapeutic concentrations, one would like to obtain these concentrations rapidly. The more rapidly the drug is absorbed, in general, the sooner the pharmacological response is achieved. 

Very few injectable dosage forms have been specifically developed and approved by FDA for intraocular use. However, the ophthalmologist uses available parenteral dosage forms to deliver antiinfectives, corti-costerioids, and anesthetic products to achieve higher therapeutic concentrations intraocularly than can ordinarily be achieved by topical or systemic administration. These unapproved or off-label uses have developed over time as part of the physician s practice of medicine. However, these drugs are usually administered by subconjunctival or retrobulbar injection and rarely are they injected directly in the eye [301]. 

Antivirals are used to treat the ocular sequelae of AIDS such as CMV retinitis. They are treated with systemic administration, but with the need for higher localized ocular therapeutic concentrations, products have been developed and approved for direct administration into the vitreous cavity. 

Achieves therapeutic concentrations for Cryptococcus neoformans therapy. 

The choice of antibiotics in CBP should include those agents that are capable of crossing the prostatic epithelium into the prostatic fluid in therapeutic concentrations and that also possess the spectrum of activity to be effective. 

The steady-state maximum plasma concentration, Cmaxss, of gentamycin and tobramycin are 6 to 10 mcg/mL. The Cmax ss of amikacin is 25 to 30 mcg/mL. The Cmin ss of both gentamycin and tobramycin is 0.5 to 1.5 mcg/mL, while that of amikacin is 5 to 8 mcg/mL. In order for these drugs to be effective, it is important to closely monitor their therapeutic concentrations. An important observation of these antibiotics is that with prolonged therapy, the Cminsl, values increase. This increase is due to the renal impairment. In the case where Cmin ss is less than the desired Cmin ss, the dose may be insufficient. 

Despite tremendous innovations in the field of drug delivery technology, oral intake remains the preferred route of drug administration, for reasons of patient convenience and therapy compliance. Compounds intended for oral administration must have adequate biopharmaceutical properties in order to achieve therapeutic concentrations at the targeted site of action. 

Opioid levels in the brain are significant within seconds to minutes after injection. As mentioned before, heroin is more lipid soluble than morphine, so a greater amount penetrates the brain. Lipid solubility and ionization are the predominant factors that determine the distribution of opioids (Mather 1987). At therapeutic concentrations, about one-third of morphine is bound to protein in the blood. 

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