Drug concentration peak plasma

Thiabendazole is rapidly absorbed after ingestion. With a standard dose, drug concentrations in plasma peak within 1-2 hours the half-life is 1.2 hours. The drug is almost completely metabolized in the liver to the 5-hydroxy form 90% is excreted in the urine in 48 hours, largely as the glucuronide or sulfonate conjugate. Thiabendazole can also be absorbed from the skin. 

Following an oral dose of 100 mg to 3 subjects, who were taking the drug regularly, peak plasma concentrations of 1.5 to 3.1 pg/ml (mean 2.2) were attained in 1.3 to 5 hours (H. W. Jun etal., ibid.). 

This may be concentration and drug dependent. t = Increase = decrease — = no effect, k, = absorption rate constant = time AUC = area under the plasma drug concentration time curve. for peak drug concentration in plasma ... 

As previously indicated, the determination of a drug concentrations in plasma specimens requires the construction of a calibration response curve. This curve is often constructed as a straight line from the measured peak response ratios (y,) plotted against their respective calibrator concentrations (x,). The drug concentration in a specimen or the apparent (back-calculated) calibrator concentration is obtained from a rearrangement of theequation for the calibration line (without error) x,- = (y,- — b)/m. An example of a calibration curve with back-calculated concentrations is given the first four columns of Table 10. 

The direct application of Eq. (23.25) to in vivo PD data assumes that drug concentrations in plasma and the biophase are in rapid equilibrium and directly proportional. Furthermore, maximum or peak effects are assumed to occur at peak drug concentrations (i.e., lack of hysteresis in concentration-effect curves). However, the operational model may be included also in indirect response models that characterize the temporal displacement between concentration and effect in mechanistic terms (26). 

Peak and trough concentrations The maximum and minimum drug concentrations—in plasma or blood—measured during cycles of repeated dosing... 

Cmax Maximum (peak) drug concentration in plasma. The C ax often correlates widi toxicity and/or efficacy. 

Opioids maybe administered in a variety of routes including oral (tablet and liquid), sublingual, rectal, transdermal, transmucosal, intravenous, subcutaneous, and intraspinal. While the oral and transdermal routes are most common, the method of administration is based on patient needs (severity of pain) and characteristics (swallowing difficulty and preference). Oral opioids have an onset of effect of 45 minutes, so intravenous or subcutaneous administration maybe preferred if more rapid relief is desired. Intramuscular injections are not recommended because of pain at the injection site and wide fluctuations in drug absorption and peak plasma concentrations achieved. More invasive routes of administration such as PCA and intraspinal (epidural and intrathecal) are primarily used postoperatively, but may also be used in refractory chronic pain situations. PCA delivers a self-administered dose via an infusion pump with a preprogrammed dose, minimum dosing interval, and maximum hourly dose. Morphine, fentanyl, and hydromorphone are commonly administered via PCA pumps by the intravenous route, but less frequently by the subcutaneous or epidural route. 

Other applications of the previously described optimization techniques are beginning to appear regularly in the pharmaceutical literature. A literature search in Chemical Abstracts on process optimization in pharmaceuticals yielded 17 articles in the 1990-1993 time-frame. An additional 18 articles were found between 1985 and 1990 for the same narrow subject. This simple literature search indicates a resurgence in the use of optimization techniques in the pharmaceutical industry. In addition, these same techniques have been applied not only to the physical properties of a tablet formulation, but also to the biological properties and the in-vivo performance of the product [30,31]. In addition to the usual tablet properties the authors studied the following pharmacokinetic parameters (a) time of the peak plasma concentration, (b) lag time, (c) absorption rate constant, and (d) elimination rate constant. The graphs in Fig. 15 show that for the drug hydrochlorothiazide, the time of the plasma peak and the absorption rate constant could, indeed, be... 

Intravenous (IV) Into a vein. Because the drug enters directly into the circulation, there is no absorption phase this means that the peak plasma concentration is reached almost immediately. This route is used when a rapid onset of action is required. 

Peak plasma levels are reached about 1.5 h after oral ingestion, the maximum concentrations being in the order of 2 - 3 ng equivalents/ml (parent drug + metabolites) for an oral 1 mg dose. The elimination from the plasma is biphasic and proceeds with mean half-lives of 6 h (a-phase) and 50 h ((3-phase). Similar elimination half-lives are obtained from the urinary excretion. The cumulative renal excretion is practically the same after oral and intravenous administration and amounts to 6 - 7 % of the radioactivity dosed. The main portion of the dose, either oral or intravenous, is eliminated by the biliary route into the faeces. The kinetics of bromocriptine has been demonstrated to be linear in the oral dose range from 2.5 to 7.5 mg. 

The plasma levels of triprolidine hydrochloride were determined in 16 normal male subjects.12 When administered orally at a concentration of 3.75 mg triprolidine hydrochloride in 15 ml of syrup, peak plasma levels of 8.2 ng/ml were achieved in 2 hours with a drug half-life of 5 hours. The low plasma levels found indicate a large volume of tissue distribution which was consistent with data obtained from rat studies. 

---